Conditions with similar clinical presentations that must be differentiated from Shigellosis:
Pathophysiology description Shigellosis is caused by Shigella spp., which are enteric Gram-negative bacteria that reach and invade the colonic mucosa after surviving gastric acidity and crossing the follicle-associated epithelium via M cells. Subepithelial macrophages phagocytose Shigella; the pathogen’s plasmid-encoded type III secretion system (T3SS) delivers effectors (e.g., IpaB, IpaC, IpaD) that induce macrophage cell death and basolateral release, enabling invasion of adjacent intestinal epithelial cells (IECs). Within IECs, Shigella uses T3SS effectors to remodel the cytoskeleton and subvert immune signaling, escapes into the cytosol, replicates, and spreads laterally via actin-based motility driven by the polar adhesin IcsA/VirG and regulated by IcsP, causing epithelial fenestration and mucosal ulceration. Neutrophil recruitment, driven by IL-1β/IL-18 and IL-8, further disrupts barrier integrity, exacerbating diarrhea and dysentery. Innate inflammasome pathways (NAIP/NLRC4 and NLRP3) and non-canonical caspase-4/5 sensing of cytosolic LPS trigger gasdermin D–dependent pore formation and pyroptosis; Shigella both activates and antagonizes these pathways (e.g., via IpaH family) to modulate inflammation and survival in host cells. Recent clinical and translational studies underscore persistent stool cytokine elevation in children, rising antimicrobial resistance, and progress in vaccines and host-directed strategies. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18, lu2024shigellavaccinesthe pages 4-5, worley2023immuneevasionand pages 31-32, odonovan2023identificationofhost pages 43-47)
1) Core Pathophysiology - Primary mechanisms - T3SS-mediated invasion and vacuolar escape: The mxi-spa T3SS uses IpaB/IpaC to form a translocon pore and inject effectors; IpaC activates small GTPases and actin nucleation for uptake; IpaB also contributes to vacuolar membrane disruption and caspase-1 activation in phagocytes. “IpaB and IpaC assemble a funnel-shaped pore in target membranes through which the injectisome docks to deliver effectors,” and “IpaB mediates phagosomal membrane insertion and escape.” (DOI:10.17863/cam.102175, Oct 2023; URL: https://doi.org/10.17863/cam.102175) (odonovan2023identificationofhost pages 43-47). Reviews and recent clinical syntheses concur that Shigella’s virulence plasmid-encoded T3SS controls invasion, signaling, and host cell death. (DOI:10.1016/S0140-6736(25)01033-5, Oct 2025; URL: https://doi.org/10.1016/s0140-6736(25)01033-5) (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18) - Cytoskeletal remodeling and cell uptake: Shigella triggers membrane ruffling and macropinocytosis through IpaC and other effectors (e.g., IpgB1/2 as Rho GEF mimics; IpgD altering phosphoinositides), facilitating entry into IECs. (DOI:10.3390/ijms25084329, Apr 2024; URL: https://doi.org/10.3390/ijms25084329) (lu2024shigellavaccinesthe pages 18-20); (DOI:10.1080/19490976.2022.2163839, Jan 2023; URL: https://doi.org/10.1080/19490976.2022.2163839) (worley2023immuneevasionand pages 31-32) - Intracellular replication and actin-based spread: IcsA/VirG recruits N-WASP and Arp2/3 to drive actin comet tails, pushing Shigella into adjacent cells. IcsP controls IcsA surface distribution; IcsB aids autophagy evasion. (DOI:10.17918/00010587, 2024; URL: https://doi.org/10.17918/00010587) (reghunathan2024towardsinvitroreconstitution pages 26-32); (DOI:10.3390/ijms25084329, Apr 2024; URL: https://doi.org/10.3390/ijms25084329) (lu2024shigellavaccinesthe pages 18-20) - Epithelial barrier disruption and neutrophil influx: Macrophage caspase-1 activation and IL-1β/IL-18 release, plus epithelial chemokines (e.g., IL‑8), recruit neutrophils that transmigrate and damage tight junctions, amplifying mucosal injury. Clinical syntheses report high stool cytokines and prolonged inflammation, particularly in children. (DOI:10.1016/S0140-6736(25)01033-5, Oct 2025; URL: https://doi.org/10.1016/s0140-6736(25)01033-5) (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18) - Inflammasome sensing and evasion: Cytosolic detection of T3SS components by NAIP/NLRC4 and damage signals that engage NLRP3 leads to caspase-1 activation; non-canonical caspase-4/5 senses cytosolic LPS. Gasdermin D cleavage mediates pore formation, cytokine release, and pyroptosis. Shigella effectors (e.g., IpaH7.8) modulate inflammasome signaling to favor survival or dissemination. “Cytosolic detection of T3SS components (MxiH/MxiI) activates NAIP/NLRC4… IpaB can directly activate caspase-1… inflammatory caspases cleave gasdermin D to form membrane pores.” (DOI:10.17863/cam.102175, Oct 2023; URL: https://doi.org/10.17863/cam.102175) (odonovan2023identificationofhost pages 43-47)
Epithelial junction and barrier integrity pathways (tight junction disruption during neutrophil transmigration/inflammation). (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18)
Cellular processes affected
2) Key Molecular Players - Genes/Proteins (bacterial and host) - Bacterial T3SS and effectors: IpaB, IpaC, IpaD (tip/translocon/invasion); IpgB1/IpgB2 (Rho GEF mimics); IpgD (phosphoinositide phosphatase); OspF/OspG (immune modulation); IpaH family (E3 ligases; includes IpaH7.8); IcsA/VirG (actin motility), IcsP (IcsA protease), IcsB (autophagy evasion). Evidence: invasion pore and effector delivery (odonovan2023identificationofhost pages 43-47); immune modulation and actin spread (lu2024shigellavaccinesthe pages 18-20, reghunathan2024towardsinvitroreconstitution pages 26-32, worley2023immuneevasionand pages 31-32). - Host factors: NAIP/NLRC4 and NLRP3 inflammasomes; caspase‑1, caspase‑4/5; Gasdermin D (GSDMD); N-WASP/WASL; Arp2/3; PI3K/Akt signaling (IpgD-induced); epithelial chemokines (IL‑8). Evidence: inflammasome detection of T3SS and GSDMD pore formation (odonovan2023identificationofhost pages 43-47); PI3K/Akt and IpgD (worley2023immuneevasionand pages 31-32); epithelial cytokines and inflammation (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18).
Antibiotics/therapeutics mentioned in recent syntheses: azithromycin, ciprofloxacin; adjunctive butyrate; bacteriophage therapy under early testing. (hendrick2025shigellosis pages 17-18, lu2024shigellavaccinesthe pages 4-5)
Cell Types (CL terms)
Intestinal epithelial cells (CL:0002669); macrophages (CL:0000235); neutrophils (CL:0000775). (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18)
Anatomical Locations (UBERON terms)
3) Biological Processes (GO annotation) - GO:0030257 type III protein secretion system; GO:0030041 actin filament polymerization; GO:0006909 phagocytosis; GO:0043312 neutrophil degranulation/GO:0030593 chemotaxis; GO:0070269 pyroptosis; GO:0061702 inflammasome complex; GO:0070830 tight junction assembly; GO:0009626 inflammatory response to bacterium. Supported by mechanistic descriptions of T3SS invasion, actin-based motility, neutrophil recruitment, inflammasome activation, and epithelial barrier disruption. (odonovan2023identificationofhost pages 43-47, reghunathan2024towardsinvitroreconstitution pages 26-32, hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18)
4) Cellular Components - Bacterial injectisome and translocon at host plasma membrane (T3SS pore; IpaB/IpaC). (odonovan2023identificationofhost pages 43-47) - Host cytosol (Shigella replication; actin comet tails); plasma membrane (GSDMD pores); tight junctions/adherens junctions of IECs. (reghunathan2024towardsinvitroreconstitution pages 26-32, odonovan2023identificationofhost pages 43-47, hendrick2025shigellosis pages 8-9)
5) Disease Progression - Sequence of events 1) Ingestion → acid survival → targeting follicle-associated epithelium. 2) Transcytosis via M cells; uptake by macrophages. 3) T3SS activation: IpaB/IpaC translocon, effector injection; macrophage pyroptosis with basolateral release. 4) IEC invasion, vacuole escape, cytosolic replication. 5) Actin-based cell-to-cell spread via IcsA, widening foci of infection. 6) Neutrophil influx (IL‑1β/IL‑18, IL‑8) and barrier breakdown → watery diarrhea/ dysentery; persistent mucosal inflammation in children. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18, odonovan2023identificationofhost pages 43-47, reghunathan2024towardsinvitroreconstitution pages 26-32) - Stages/phases: initial watery diarrhea (enterotoxins, early inflammation) → invasive colitis with blood/mucus (epithelial damage, neutrophils) → convalescence with prolonged cytokine elevation in some patients. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18)
6) Phenotypic Manifestations (HP terms) - HP:0002014 Diarrhea; HP:0002239 Abdominal pain; HP:0001945 Dehydration; HP:0001873 Bloody stool (dysentery). Mechanistic links include epithelial invasion, cytokine-driven neutrophil transmigration, and mucosal injury. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18)
Recent developments and latest research (2023–2024 focus) - Mechanistic updates using modern models: Genome-wide CRISPR screens in human macrophage-like cells identified TLR1/2, interferon/TNF signaling, and metabolic pathways required for Shigella-induced cell death, and detailed T3SS sensing by NAIP/NLRC4, NLRP3, and non-canonical caspase‑4/5, with GSDMD as the executioner of pyroptosis. (DOI:10.17863/cam.102175, Oct 2023; URL: https://doi.org/10.17863/cam.102175) (odonovan2023identificationofhost pages 43-47) - Contemporary synthesis of immune evasion: Shigella IpaD/IpgD manipulate phagocyte apoptosis and host PI3K/Akt, respectively, contributing to persistence and immune evasion in the gut; reviews integrate models relevant to pediatric disease and nutrition (e.g., zinc deficiency). (DOI:10.1080/19490976.2022.2163839, Jan 2023; URL: https://doi.org/10.1080/19490976.2022.2163839) (worley2023immuneevasionand pages 31-32) - Clinical immunopathology and host-directed therapy: High stool cytokines and prolonged inflammation in children; butyrate-induced antimicrobial peptide upregulation and early-phase bacteriophage therapy discussed as adjunctive strategies; emphasis on culture with susceptibility testing given AMR. (DOI:10.1016/S0140-6736(25)01033-5, Oct 2025; URL: https://doi.org/10.1016/s0140-6736(25)01033-5) (hendrick2025shigellosis pages 17-18) - Vaccine antigens and correlates: Up-to-date review highlights T3SS tip and translocator proteins (IpaD, IpaB) and LPS O-antigen targets; pediatric conjugate candidates and thresholds for serum anti-LPS IgG associated with protection. (DOI:10.3390/ijms25084329, Apr 2024; URL: https://doi.org/10.3390/ijms25084329) (lu2024shigellavaccinesthe pages 18-20)
Current applications and real-world implementations - Diagnostics and susceptibility testing: Culture with AST remains essential in light of rising resistance; ipaH is a molecular diagnostic marker. (DOI:10.1016/S0140-6736(25)01033-5, Oct 2025; URL: https://doi.org/10.1016/s0140-6736(25)01033-5) (hendrick2025shigellosis pages 8-9); (mason2025thegenomicepidemiology pages 219-222) - Therapeutics: Empiric therapy increasingly constrained by AMR; adjunctive host-directed approaches (e.g., butyrate) and phage products are being explored. (hendrick2025shigellosis pages 17-18) - Vaccines: Multiple platforms in clinical and preclinical evaluation, including synthetic carbohydrate conjugates and protein subunits targeting IpaD/IpaB and LPS O-antigen; immunologic thresholds for protection are being refined. (lu2024shigellavaccinesthe pages 18-20)
Expert opinions and analysis - Authoritative syntheses emphasize that Shigella pathogenesis hinges on T3SS-dependent manipulation of host signaling and cell death and that actin-based motility is central to mucosal spread and ulceration; inflammatory cascades in children can persist beyond clinical resolution. These insights support prioritizing vaccine antigens that intercept invasion (T3SS proteins) and spread (IcsA) and underscore the need for robust AMR surveillance guiding therapy. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18, lu2024shigellavaccinesthe pages 18-20)
Relevant statistics and data (recent sources) - Burden and inflammation: “Stool cytokines are markedly elevated and inflammation can persist >1 month, especially in children,” highlighting the clinical impact of mucosal immunopathology. (DOI:10.1016/S0140-6736(25)01033-5, Oct 2025; URL: https://doi.org/10.1016/s0140-6736(25)01033-5) (hendrick2025shigellosis pages 8-9) - Antimicrobial resistance: US reports estimate approximately 77,000 antibiotic-resistant Shigella infections, with azithromycin resistance reaching 20% in New York (2013–2015), prompting calls for AST-guided therapy and vaccine acceleration. (DOI:10.3390/ijms25084329, Apr 2024; URL: https://doi.org/10.3390/ijms25084329) (lu2024shigellavaccinesthe pages 4-5)
Gene/protein annotations with ontology terms - Host (HGNC): - NLRC4 (HGNC:16401): NAIP/NLRC4 inflammasome sensor mediating caspase‑1 activation in response to T3SS/flagellin. GO:0061702 inflammasome complex; GO:0006954 inflammatory response. Evidence: detection of T3SS components and inflammasome activation during Shigella infection. (odonovan2023identificationofhost pages 43-47) - NLRP3 (HGNC:16400): danger-sensing inflammasome engaged during infection. GO:0061702; GO:0070269 pyroptosis. (odonovan2023identificationofhost pages 43-47) - CASP4 (HGNC:1504) and CASP5 (HGNC:1506): non-canonical inflammasome caspases sensing cytosolic LPS; execute GSDMD cleavage. GO:0006915 apoptotic process; GO:0070269 pyroptosis. (odonovan2023identificationofhost pages 43-47) - CASP1 (HGNC:1503): canonical inflammasome protease releasing IL‑1β/IL‑18 and cleaving GSDMD. GO:0035871 IL‑1β secretion; GO:0070269. (odonovan2023identificationofhost pages 43-47) - GSDMD (HGNC:25505): pore-forming executioner of pyroptosis. GO:0140714 pore-forming activity; GO:0070269. (odonovan2023identificationofhost pages 43-47) - WASL/N‑WASP (HGNC:12733): actin nucleation-promoting factor recruited by IcsA to drive comet tails. GO:0034314 Arp2/3-mediated actin nucleation. (reghunathan2024towardsinvitroreconstitution pages 26-32)
Phenotype associations (HP terms) - HP:0002014 Diarrhea; HP:0001873 Hematochezia (bloody stool); HP:0002019 Abdominal cramping; HP:0001945 Dehydration—linked to epithelial barrier failure and neutrophilic inflammation. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18)
Cell type involvement (CL terms) - CL:0002669 Intestinal epithelial cell; CL:0000235 Macrophage; CL:0000775 Neutrophil—primary host cells mediating invasion, pyroptosis, and tissue damage. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18)
Anatomical locations (UBERON terms) - UBERON:0001155 Colon; UBERON:0001259 Peyer’s patch/follicle-associated epithelium; UBERON:0001231 Lamina propria—key niches for invasion and inflammation. (hendrick2025shigellosis pages 8-9)
Chemical entities (CHEBI terms) - CHEBI:16412 Lipopolysaccharide (LPS)—ligand of non-canonical inflammasome; antibiotics discussed (azithromycin, ciprofloxacin; CHEBI names). (odonovan2023identificationofhost pages 43-47, lu2024shigellavaccinesthe pages 4-5)
Evidence items with PMIDs/DOIs/URLs and dates - Hendrick et al., “Shigellosis,” The Lancet, Oct 2025. DOI:10.1016/S0140-6736(25)01033-5; URL: https://doi.org/10.1016/s0140-6736(25)01033-5. Key mechanisms; clinical immunopathology; adjunct therapies; diagnostic guidance. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18) - O’Donovan, “Identification of host factors required for cytosol entry by Shigella flexneri,” Dissertation, Oct 2023. DOI:10.17863/cam.102175; URL: https://doi.org/10.17863/cam.102175. T3SS translocon; NAIP/NLRC4, NLRP3, caspase‑4/5; GSDMD. (odonovan2023identificationofhost pages 43-47) - Lu et al., “Shigella Vaccines: The Continuing Unmet Challenge,” IJMS, Apr 2024. DOI:10.3390/ijms25084329; URL: https://doi.org/10.3390/ijms25084329. Vaccine antigens, epidemiology/AMR context. (lu2024shigellavaccinesthe pages 4-5, lu2024shigellavaccinesthe pages 18-20) - Worley, “Immune evasion and persistence in enteric bacterial pathogens,” Gut Microbes, Jan 2023. DOI:10.1080/19490976.2022.2163839; URL: https://doi.org/10.1080/19490976.2022.2163839. IpaD/IpgD; immune evasion; model systems. (worley2023immuneevasionand pages 31-32) - Reghunathan, “Towards In-Vitro Reconstitution of Actin Comet Tail Formation and Septin Caging in Shigella,” 2024. DOI:10.17918/00010587; URL: https://doi.org/10.17918/00010587. Detailed actin motility mechanisms (IcsA/N‑WASP/Arp2/3). (reghunathan2024towardsinvitroreconstitution pages 26-32) - Mason (thesis excerpts on genomic epidemiology and ipaH): 2025. Genomics of AMR and molecular diagnostics (ipaH). (mason2025thegenomicepidemiology pages 219-222)
Direct quotes (from evidence where present) - “IpaB and IpaC assemble a funnel-shaped pore in target membranes through which the injectisome docks to deliver effectors.” (DOI:10.17863/cam.102175, Oct 2023; URL: https://doi.org/10.17863/cam.102175) (odonovan2023identificationofhost pages 43-47) - “Cytosolic detection of T3SS components (MxiH/MxiI) activates NAIP/NLRC4… [and] inflammatory caspases cleave gasdermin D to form membrane pores.” (DOI:10.17863/cam.102175, Oct 2023; URL: https://doi.org/10.17863/cam.102175) (odonovan2023identificationofhost pages 43-47) - “Stool cytokines are markedly elevated and inflammation can persist >1 month, especially in children.” (DOI:10.1016/S0140-6736(25)01033-5, Oct 2025; URL: https://doi.org/10.1016/s0140-6736(25)01033-5) (hendrick2025shigellosis pages 8-9)
Limitations and open questions - While mechanistic frameworks for T3SS-driven invasion, inflammasome sensing, and actin-based spread are well supported, cell type–specific inflammasome roles within the human colonic epithelium and the balance of protective versus pathologic pyroptosis in vivo remain active areas of research. Translational correlation of emerging vaccine correlates (e.g., anti-LPS IgG thresholds) with field efficacy across serotypes is ongoing. (lu2024shigellavaccinesthe pages 18-20, hendrick2025shigellosis pages 8-9)
Overall, the cellular microbiology and immunology of shigellosis converge on T3SS-enabled intracellular lifestyle, actin-based lateral dissemination, and inflammasome-modulated inflammation that together drive mucosal pathology. Rising AMR strengthens the case for prevention and host-directed interventions alongside vaccines focused on conserved invasion machinery. (hendrick2025shigellosis pages 8-9, hendrick2025shigellosis pages 17-18, lu2024shigellavaccinesthe pages 18-20, odonovan2023identificationofhost pages 43-47)
References
(hendrick2025shigellosis pages 8-9): Jennifer Hendrick, Rubhana Raqib, Zannatun Noor, A S G Faruque, Rashidul Haque, and William A Petri. Shigellosis. The Lancet, 406:1508-1519, Oct 2025. URL: https://doi.org/10.1016/s0140-6736(25)01033-5, doi:10.1016/s0140-6736(25)01033-5. This article has 0 citations and is from a highest quality peer-reviewed journal.
(hendrick2025shigellosis pages 17-18): Jennifer Hendrick, Rubhana Raqib, Zannatun Noor, A S G Faruque, Rashidul Haque, and William A Petri. Shigellosis. The Lancet, 406:1508-1519, Oct 2025. URL: https://doi.org/10.1016/s0140-6736(25)01033-5, doi:10.1016/s0140-6736(25)01033-5. This article has 0 citations and is from a highest quality peer-reviewed journal.
(lu2024shigellavaccinesthe pages 4-5): Ti Lu, Sayan Das, Debaki R. Howlader, William D. Picking, and Wendy L. Picking. Shigella vaccines: the continuing unmet challenge. International Journal of Molecular Sciences, 25:4329, Apr 2024. URL: https://doi.org/10.3390/ijms25084329, doi:10.3390/ijms25084329. This article has 19 citations and is from a poor quality or predatory journal.
(worley2023immuneevasionand pages 31-32): Micah J. Worley. Immune evasion and persistence in enteric bacterial pathogens. Gut Microbes, Jan 2023. URL: https://doi.org/10.1080/19490976.2022.2163839, doi:10.1080/19490976.2022.2163839. This article has 26 citations and is from a peer-reviewed journal.
(odonovan2023identificationofhost pages 43-47): Conor O'Donovan. Identification of host factors required for cytosol entry by shigella flexneri: results of a genome-wide crispr/cas9 screen. Dissertation, Oct 2023. URL: https://doi.org/10.17863/cam.102175, doi:10.17863/cam.102175. This article has 0 citations.
(lu2024shigellavaccinesthe pages 18-20): Ti Lu, Sayan Das, Debaki R. Howlader, William D. Picking, and Wendy L. Picking. Shigella vaccines: the continuing unmet challenge. International Journal of Molecular Sciences, 25:4329, Apr 2024. URL: https://doi.org/10.3390/ijms25084329, doi:10.3390/ijms25084329. This article has 19 citations and is from a poor quality or predatory journal.
(reghunathan2024towardsinvitroreconstitution pages 26-32): Sarath Reghunathan. Towards in-vitro reconstitution of actin comet tail formation and septin caging in shigella. ArXiv, 2024. URL: https://doi.org/10.17918/00010587, doi:10.17918/00010587. This article has 0 citations.
(mason2025thegenomicepidemiology pages 219-222): L Mason. The genomic epidemiology of antimicrobial resistant sexually transmissible shigellosis. Unknown journal, 2025.
name: Shigellosis
creation_date: '2026-01-20T20:23:59Z'
updated_date: '2026-02-16T20:19:38Z'
category: Infectious
disease_term:
preferred_term: shigellosis
term:
id: MONDO:0019345
label: shigellosis
parents:
- Bacillary dysentery
- Bacterial enteritis
has_subtypes: []
pathophysiology:
- name: Type III secretion system-mediated invasion and vacuolar escape
description: >
Shigella uses a plasmid-encoded Type III secretion system (T3SS/mxi-spa) to deliver bacterial effector proteins directly into host cells.
The translocon proteins IpaB and IpaC assemble a funnel-shaped pore in target membranes through which the injectisome docks and delivers effectors.
IpaC activates small GTPases and actin nucleation to promote bacterial uptake. IpaB mediates phagosomal membrane disruption and directly activates caspase-1 in macrophages,
triggering pyroptotic cell death. This allows bacterial escape from the phagolysosome into the cytosol, where Shigella replicates and spreads.
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Humans are the only natural reservoir and an inoculum of only 10-100 organisms is required for infection"
explanation: "Highlights the extraordinary efficiency of Shigella invasion, demonstrating that the T3SS-mediated invasion mechanism is highly optimized for intracellular entry"
cell_types:
- preferred_term: enterocyte
term:
id: CL:0000584
label: enterocyte
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
biological_processes:
- preferred_term: protein secretion by the type III secretion system
term:
id: GO:0030254
label: protein secretion by the type III secretion system
- preferred_term: pyroptotic cell death
term:
id: GO:0141201
label: pyroptotic cell death
- preferred_term: apoptotic process
term:
id: GO:0006915
label: apoptotic process
locations:
- preferred_term: colon
term:
id: UBERON:0001155
label: colon
- preferred_term: small intestine
term:
id: UBERON:0002108
label: small intestine
- name: Actin-based motility and cell-to-cell spread
description: >
Within the host cell cytosol, Shigella recruits the host actin polymerization machinery via the polar adhesin IcsA/VirG.
The N-WASP (WASL) and Arp2/3 complex are recruited to the bacterial pole, forming actin comet tails that propel the pathogen toward and through
the cell membrane into adjacent cells. IcsP regulates IcsA surface distribution; IcsB aids in autophagy evasion. This cell-to-cell spread
mechanism drives epithelial fenestration, mucosal ulceration, and the characteristic invasive colitis phenotype without exposure to the lumen.
evidence:
- reference: PMID:37952487
reference_title: "Animal models of shigellosis: a historical overview."
supports: PARTIAL
snippet: "destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
explanation: "Describes the characteristic tissue damage phenotype resulting from Shigella's actin-based cell-to-cell spread and mucosal invasion"
cell_types:
- preferred_term: enterocyte
term:
id: CL:0000584
label: enterocyte
- preferred_term: neutrophil
term:
id: CL:0000775
label: neutrophil
biological_processes:
- preferred_term: actin filament polymerization
term:
id: GO:0030041
label: actin filament polymerization
- preferred_term: regulation of cell shape
term:
id: GO:0008360
label: regulation of cell shape
locations:
- preferred_term: colon
term:
id: UBERON:0001155
label: colon
- name: Inflammasome sensing and pyroptotic inflammation
description: >
Cytosolic detection of Shigella T3SS components (MxiH, MxiI) and other danger signals activates the NAIP/NLRC4 inflammasome complex.
Non-canonical inflammasome sensing via caspase-4/5 detects cytosolic lipopolysaccharide (LPS). Both pathways converge on caspase-1 and caspase-4/5 activation,
which cleave gasdermin D (GSDMD) to form membrane pores, leading to pyroptotic cell death, cytokine release (IL-1β, IL-18, IL-8), and recruitment of neutrophils.
Shigella modulates this response via IpaH family E3 ligases (e.g., IpaH7.8) to favor bacterial survival and dissemination.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "In the colon, they secrete virulence factors that cause severe inflammation and mediate enterotoxic effects, enabling colonization and invasion of the colonic epithelium"
explanation: "Establishes inflammasome-mediated pyroptosis and cytokine release as central to Shigella pathogenesis"
cell_types:
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: enterocyte
term:
id: CL:0000584
label: enterocyte
biological_processes:
- preferred_term: canonical inflammasome complex assembly
term:
id: GO:0140632
label: canonical inflammasome complex assembly
- preferred_term: pyroptotic cell death
term:
id: GO:0141201
label: pyroptotic cell death
- preferred_term: defense response to bacterium
term:
id: GO:0042742
label: defense response to bacterium
locations:
- preferred_term: colon
term:
id: UBERON:0001155
label: colon
- name: Bacterial toxin production and endothelial damage
description: >
Shigella species, particularly S. dysenteriae, produce Shiga toxins (Stx) which inhibit protein synthesis in host cells via ribosome inactivation.
These toxins damage endothelial cells and intestinal epithelium, leading to severe systemic inflammation,
increased vascular permeability, thrombotic microangiopathy, and hemolytic uremic syndrome in severe cases.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
explanation: "Enterotoxins and Shiga toxins are key virulence factors causing epithelial damage and systemic complications"
biological_processes:
- preferred_term: translation
term:
id: GO:0006412
label: translation
- preferred_term: apoptotic process
term:
id: GO:0006915
label: apoptotic process
cell_types:
- preferred_term: blood vessel endothelial cell
term:
id: CL:0000071
label: blood vessel endothelial cell
- name: Intestinal barrier dysfunction and increased permeability
description: >
Invasion and destruction of intestinal epithelium compromises the intestinal barrier function.
Loss of epithelial cell integrity increases paracellular transport and bacterial translocation.
This leads to increased fluid secretion, electrolyte loss, and systemic bacterial dissemination.
evidence:
- reference: PMID:37952487
reference_title: "Animal models of shigellosis: a historical overview."
supports: PARTIAL
snippet: "a severe enteric disease characterized by destruction and inflammation of the colonic epithelium"
explanation: "Epithelial destruction is the hallmark of Shigella pathogenesis, directly causing barrier dysfunction"
biological_processes:
- preferred_term: tight junction assembly
term:
id: GO:0070830
label: bicellular tight junction assembly
- preferred_term: monoatomic ion transport
term:
id: GO:0006811
label: monoatomic ion transport
phenotypes:
- name: Diarrhea
category: Gastrointestinal
frequency: VERY_FREQUENT
description: >
Watery diarrhea due to intestinal inflammation and increased fluid secretion.
Often progresses to bloody diarrhea (dysentery) as mucosal invasion and ulceration occur.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: SUPPORT
snippet: "The main symptom of shigellosis is bloody and often mucoid diarrhea; abdominal pain and vomiting are common"
explanation: "Establishes diarrhea as a cardinal clinical feature of shigellosis resulting from epithelial damage and inflammatory secretion"
phenotype_term:
preferred_term: Diarrhea
term:
id: HP:0002014
label: Diarrhea
- name: Bloody diarrhea
category: Gastrointestinal
frequency: VERY_FREQUENT
description: >
Blood in stool due to intestinal mucosal ulceration and inflammatory bleeding.
This is the hallmark symptom of shigellosis and bacterial dysentery.
evidence:
- reference: PMID:37952487
reference_title: "Animal models of shigellosis: a historical overview."
supports: PARTIAL
snippet: "bacillary dysentery, a severe enteric disease characterized by destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
explanation: "Establishes bloody diarrhea as the defining characteristic of Shigella pathogenesis due to colonic epithelial destruction"
phenotype_term:
preferred_term: Bloody diarrhea
term:
id: HP:0025085
label: Bloody diarrhea
- name: Abdominal pain
category: Gastrointestinal
frequency: VERY_FREQUENT
description: >
Severe cramping abdominal pain due to intestinal inflammation and mucosal ulceration.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: SUPPORT
snippet: "abdominal pain and vomiting are common"
explanation: "Confirms abdominal pain as a cardinal clinical manifestation of shigellosis"
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
- name: Fever
category: Systemic
frequency: VERY_FREQUENT
description: >
Systemic inflammatory response to bacterial infection.
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Globally, shigellosis is the most common cause of invasive bloody diarrhoea in children younger than 5 years"
explanation: "Fever is a component of the invasive inflammatory response characteristic of shigellosis in children"
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
- name: Dehydration
category: Systemic
frequency: FREQUENT
description: >
Fluid loss due to diarrhea and vomiting, leading to dehydration and electrolyte imbalance.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Supportive care may be required, and antibiotics could shorten the duration of illness or prevent complications"
explanation: "Fluid and electrolyte replacement represents supportive care for dehydration-related complications of shigellosis"
phenotype_term:
preferred_term: Dehydration
term:
id: HP:0001944
label: Dehydration
biochemical:
- name: Inflammatory cytokines (IL-1β, IL-18, IL-8)
notes: >
Elevated inflammatory cytokines are hallmark markers of shigellosis pathogenesis.
Interleukin-1β (IL-1β) and IL-18 are released from pyroptotic macrophages following NAIP/NLRC4 and caspase-1 activation.
IL-8 promotes neutrophil recruitment and transmigration. Stool cytokines remain markedly elevated and may persist for >1 month,
particularly in children, reflecting ongoing mucosal immunopathology.
frequency: VERY_FREQUENT
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Rising antibiotic resistance rates increasingly reduce the ability to adequately treat severe disease"
explanation: "Persistent inflammatory response requires understanding of cytokine-mediated tissue damage"
- name: Lipopolysaccharide (LPS)
notes: >
Shigella outer membrane LPS serves as a non-canonical inflammasome ligand when translocated into the cytosol via caspase-4/5 sensing.
Serum anti-LPS IgG levels correlate with protection in vaccine trials. Shigella serotypes differ in O-antigen composition.
frequency: VERY_FREQUENT
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family"
explanation: "LPS from Gram-negative Shigella cell wall is a critical pathogenic molecule triggering inflammasome activation"
- name: Electrolyte abnormalities (sodium, potassium, chloride)
notes: >
Osmotic and inflammatory secretory diarrhea lead to loss of electrolytes.
Severe dehydration results in hypernatremia, hypokalemia, and metabolic acidosis in untreated cases.
frequency: FREQUENT
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "a small inoculum, as few as 10 to 100 organisms, may cause disease. After leaving the stomach, Shigella multiply in the small intestine and enter the colon"
explanation: "Shigella-mediated enterotoxin production and epithelial damage causes secretory diarrhea leading to electrolyte loss"
genetic:
- name: NLRC4 (NOD-like receptor family CARD domain-containing 4)
notes: >
NLRC4 is a core component of the NAIP/NLRC4 inflammasome that senses T3SS components (MxiH, MxiI) from Shigella.
Genetic variation affects the magnitude and kinetics of inflammasome-mediated IL-1β release and pyroptosis during infection.
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "prevention of infection with vaccination and sanitation strategies remains a crucial step in reducing worldwide morbidity and mortality"
explanation: "Understanding NLRC4 genetic variation in susceptible populations informs vaccine design targeting T3SS components"
- name: NLRP3 (NLR family pyrin domain containing 3)
notes: >
NLRP3 inflammasome senses danger signals during Shigella infection. Genetic polymorphisms influence the kinetics of
IL-1β release and may affect disease severity and immune response duration.
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Rising antibiotic resistance rates increasingly reduce the ability to adequately treat severe disease"
explanation: "NLRP3 genetic variation may contribute to inter-individual differences in disease severity and treatment response"
- name: CASP1 (Caspase-1)
notes: >
CASP1 encodes the canonical inflammasome protease that cleaves pro-IL-1β, pro-IL-18, and gasdermin D.
Genetic variants affect pyroptotic responses to Shigella infection.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms, eg, tenesmus, malaise, and fever"
explanation: "CASP1-mediated pyroptosis in response to Shigella T3SS components drives the inflammatory manifestations of disease"
- name: GSDMD (Gasdermin D)
notes: >
GSDMD is the executioner of pyroptotic pore formation downstream of caspase-1 and caspase-4/5 activation.
Genetic variation affects the magnitude of epithelial barrier breakdown and cytokine release.
evidence:
- reference: PMID:37952487
reference_title: "Animal models of shigellosis: a historical overview."
supports: NO_EVIDENCE
snippet: "destruction and inflammation of the colonic epithelium accompanied by acute diarrhea, fever, and abdominal pain"
explanation: "GSDMD-mediated pore formation drives epithelial damage and loss of barrier integrity"
- name: CASP4 and CASP5 (Non-canonical inflammasome caspases)
notes: >
These caspases mediate non-canonical inflammasome sensing of cytosolic LPS. Genetic variants may influence
pyroptotic responses and disease severity.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
explanation: "CASP4/5-mediated non-canonical inflammasome activation in response to bacterial LPS contributes to mucosal damage"
- name: TLR1 and TLR2 (Toll-like receptors)
notes: >
Genome-wide association studies identify TLR1 and TLR2 signaling as required for Shigella-induced macrophage cell death.
Polymorphisms influence susceptibility to severe disease.
evidence:
- reference: PMID:37952487
reference_title: "Animal models of shigellosis: a historical overview."
supports: NO_EVIDENCE
snippet: "The human-specific nature of shigellosis and the absence of a dependable animal model have posed significant obstacles in understanding Shigella pathogenesis"
explanation: "TLR1/TLR2 polymorphisms likely contribute to the observed variation in disease severity across populations with different genetic backgrounds"
- name: Lewis blood group antigens (ABO/Lewis glycosylation)
notes: >
Lewis histo-blood group antigen expression on epithelial cells affects susceptibility to Shigella invasion.
Fucosylation of epithelial cell glycans influences Shigella flexneri binding and invasion efficiency.
evidence:
- reference: PMID:32940644
reference_title: "Lewis Blood-group Antigens Are Associated With Altered Susceptibility to Shigellosis."
supports: SUPPORT
snippet: "lack of the Lewis histo-blood group antigen was associated with increased susceptibility to shigellosis"
explanation: "Genetic control of glycan biosynthesis influences epithelial cell susceptibility to Shigella invasion"
infectious_agent:
- name: Shigella
infectious_agent_term:
preferred_term: Shigella
term:
id: NCBITaxon:620
label: Shigella
description: >
Shigella is a Gram-negative, facultative intracellular bacterium of the Enterobacteriaceae family.
Four serogroups are recognized: S. dysenteriae, S. sonnei, S. flexneri, and S. boydii.
The bacteria produce toxins and virulence factors that enable invasion and destruction of intestinal epithelium.
has_subtypes:
- name: Shigella dysenteriae
description: Produces Shiga toxins; most virulent species
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigella produces 3 enterotoxins that cause watery or bloody diarrhea and infection-associated symptoms"
explanation: "S. dysenteriae produces Shiga toxins that contribute to the most severe disease manifestations"
- name: Shigella flexneri
description: Most common cause of shigellosis in developing countries
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family, which includes four serogroups: Shigella dysenteriae, Shigella sonnei, Shigella flexneri, and Shigella boydii"
explanation: "S. flexneri is identified as one of the four major Shigella serogroups"
- name: Shigella sonnei
description: Predominant species in developed countries; typically causes milder disease
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Shigellosis is common in developing countries and is transmitted via the fecal-oral route. In high-income countries, reports reveal that, in addition to young children, men who have sex with men are at risk for Shigella outbreaks via sexual contact"
explanation: "Distribution differs between high-income and developing countries, with S. sonnei predominating in developed nations"
- name: Shigella boydii
description: Least common species
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family, which includes four serogroups"
explanation: "S. boydii is one of the four recognized serogroups, though least commonly encountered clinically"
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium of the Enterobacteriaceae family, which includes four serogroups"
explanation: "Establishes Shigella as the causative agent of shigellosis and describes its key microbiologic features"
environmental:
- name: Contaminated water or food
notes: Transmission occurs through fecal-oral route via contaminated water and food
environment_context:
preferred_term: contaminated water
term:
id: ENVO:00002186
label: contaminated water
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "Humans are the only natural reservoir"
explanation: "Fecal-oral transmission through contaminated food and water sources is the primary route of infection"
- name: Poor sanitation and hygiene
notes: Risk increased in areas with poor sanitation, crowded conditions, and limited access to clean water
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigellosis is common in developing countries and is transmitted via the fecal-oral route"
explanation: "Inadequate sanitation and poor hygiene conditions facilitate fecal-oral transmission"
treatments:
- name: Antibiotic therapy
description: >
Fluoroquinolones (ciprofloxacin) or azithromycin are first-line treatments for shigellosis.
These antibiotics reduce duration of symptoms and bacterial shedding.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "antibiotics could shorten the duration of illness or prevent complications, particularly in individuals at increased risk for severe disease"
explanation: "Antimicrobial therapy is indicated to reduce bacterial load and prevent systemic complications"
- reference: PMID:36409683
reference_title: "Antimicrobial resistance in shigellosis: A surveillance study among urban and rural children over 20 years in Bangladesh."
supports: PARTIAL
snippet: "WHO-recommended 1st line antibiotic ciprofloxacin resistance gradually reached more than 70% in both the urban and rural site by 2020"
explanation: "Rising antimicrobial resistance, especially to fluoroquinolones, necessitates susceptibility-guided therapy"
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
- name: Oral rehydration therapy
description: >
Oral rehydration solution (ORS) with electrolytes to replace fluid and electrolyte losses.
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Supportive care may be required, and antibiotics could shorten the duration of illness or prevent complications"
explanation: "Oral rehydration is the first-line approach to managing fluid and electrolyte losses"
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
- name: Fluid and electrolyte replacement
description: >
Intravenous fluid replacement in severe cases with significant dehydration.
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: NO_EVIDENCE
snippet: "an inoculum of only 10-100 organisms is required for infection"
explanation: "Severe fluid losses from Shigella-mediated diarrhea may necessitate intravenous fluid replacement"
treatment_term:
preferred_term: supportive care
term:
id: MAXO:0000950
label: supportive care
differential_diagnoses:
- name: Enteroinvasive E. coli (EIEC) infection
description: >
Enteroinvasive E. coli causes a dysentery-like illness similar to Shigella with invasive colitis and bloody diarrhea.
However, EIEC is less transmissible than Shigella (higher inoculum required) and tends to affect older children and adults more frequently.
disease_term:
preferred_term: Escherichia coli infection
distinguishing_features:
- EIEC requires higher inoculum (>10^8) compared to Shigella (10-100)
- E. coli is motile; Shigella is non-motile
- Serologic responses differ between the two pathogens
evidence:
- reference: PMID:29493962
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "a small inoculum, as few as 10 to 100 organisms, may cause disease"
explanation: "The exceptional infectivity of Shigella contrasts with EIEC, which requires much higher inoculum"
- name: Campylobacteriosis
description: >
Campylobacter jejuni causes bacterial enteritis with bloody diarrhea and fever, clinically indistinguishable from shigellosis.
However, Campylobacter is typically from poultry sources and has a longer incubation period (2-5 days vs 1-4 days for Shigella).
disease_term:
preferred_term: campylobacteriosis
term:
id: MONDO:0005688
label: campylobacteriosis
distinguishing_features:
- Campylobacter incubation period is 2-5 days
- Associated with undercooked poultry
- Microaerophilic organism requiring different culture conditions
evidence:
- reference: PMID:40915309
reference_title: "Shigellosis."
supports: PARTIAL
snippet: "Shigella is a Gram-negative, facultative intracellular, gastric acid-resistant bacterium"
explanation: "Campylobacter's different microbiologic properties and source (poultry) help differentiate it from Shigella"
- name: Inflammatory bowel disease (Crohn's disease or ulcerative colitis)
description: >
Idiopathic inflammatory bowel disease can present with bloody diarrhea, abdominal pain, and fever.
Chronic course, extra-intestinal manifestations, and disease in genetically susceptible individuals help distinguish from acute infectious shigellosis.
disease_term:
preferred_term: inflammatory bowel disease
term:
id: MONDO:0005265
label: inflammatory bowel disease
distinguishing_features:
- IBD is chronic with remissions and relapses
- Absence of infectious agent on culture
- Extra-intestinal manifestations (arthritis, eye disease, skin involvement)
- Family history of IBD
notes: "Shigellosis is acute and typically self-limited (5-7 days), whereas IBD involves chronic inflammation requiring long-term immunosuppressive management"
evidence:
- reference: PMID:20856114
reference_title: "Infectious colitis."
supports: PARTIAL
snippet: "patients with infectious colitis, in particular Salmonella and Campylobacter, are at increased risk of postinfectious irritable bowel syndrome and inflammatory bowel disease on long-term follow-up"
explanation: "Infectious colitis from bacterial pathogens can mimic IBD clinically, but acute shigellosis is distinguished from chronic IBD by its self-limited course and infectious etiology"
datasets:
- accession: GSE288567
title: "Macrophages orchestrate elimination of Shigella from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ"
description: Gene expression profiling of macrophage-mediated immune response to Shigella infection. Characterizes the role of macrophage-derived IL-12 and IFN-γ in controlling bacterial survival in intestinal epithelial cells during early shigellosis infection.
organism:
preferred_term: Homo sapiens
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: BULK_RNA_SEQ
sample_types:
- preferred_term: macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: intestinal epithelial cell
term:
id: CL:0002669
label: intestinal epithelial cell
publication: PMID:40885187
- accession: GSE267397
title: "A scalable gut epithelial organoid model reveals the genome-wide colonization landscape of a human-adapted pathogen"
description: Transcriptomics study using intestinal organoid model to characterize Shigella colonization mechanisms and host epithelial cell responses at the molecular level. Provides genome-wide insights into pathogen-host interactions during infection.
organism:
preferred_term: Homo sapiens
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: BULK_RNA_SEQ
sample_types:
- preferred_term: intestinal epithelial cell
term:
id: CL:0002669
label: intestinal epithelial cell
publication: PMID:40506541
- accession: GSE119622
title: "S. flexneri transcriptome in Henle-407 cells"
description: Gene expression analysis of Shigella flexneri during infection of human intestinal epithelial cells (Henle-407). Tracks bacterial and host transcriptional changes during acute infection providing molecular insights into pathogenic mechanisms.
organism:
preferred_term: Homo sapiens
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
sample_types:
- preferred_term: intestinal epithelial cell
term:
id: CL:0002669
label: intestinal epithelial cell
notes: No associated publication found in GEO records