Pneumocystis Pneumonia

Infectious Disease MONDO:0005923 Pathograph 8 Show in embeddings browser Fungal Respiratory Infection

Pneumocystis pneumonia (PCP/PJP) is an opportunistic fungal pneumonia caused by Pneumocystis jirovecii, occurring almost exclusively in hosts with impaired cell-mediated immunity. Risk factors include HIV infection (classically with CD4 counts <200 cells/µL), solid-organ transplantation, malignancy, and inflammatory or rheumatologic conditions and their immunosuppressive therapies. The organism attaches to the alveolar epithelium and produces a diffuse alveolar pneumonia with hypoxemia. First-line therapy and prophylaxis is trimethoprim-sulfamethoxazole, which targets the folate-synthesis pathway; adjunctive corticosteroids reduce mortality in hypoxemic HIV-associated disease.

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🏷

Classifications

Harrison's Part
INFECTIOUS DISEASES RESPIRATORY
⚙

Pathophysiology

3
Opportunistic Infection in Cell-Mediated Immunodeficiency
Pneumocystis jirovecii is an opportunistic fungal pathogen that causes severe pneumonia in immunocompromised hosts. Disease requires impaired cell-mediated immunity — HIV (where CD4+ T-cell depletion <200 cells/µL is the classic marker), organ transplantation, malignancy, and inflammatory/rheumatologic conditions and their immunosuppressive therapies (which impair broader cell-mediated immunity beyond CD4 count alone) — permitting uncontrolled alveolar replication.
CD4-positive, alpha-beta T cell CL:0000624 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves CD4-positive, alpha-beta T cell (CL:0000624). CL:0000624 is a cell type from the Cell Ontology.
symbiont entry into host cell GO:0046718 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves symbiont entry into host cell (GO:0046718). GO:0046718 is a biological process from the Gene Ontology.
lung UBERON:0002048 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lung (UBERON:0002048). UBERON:0002048 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Alveolar Pneumonia and Respiratory Compromise Uncontrolled alveolar replication produces a diffuse pneumonia with impaired gas exchange.
Show evidence (3 references)
PMID:33870843 SUPPORT Other
"Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts."
Establishes P. jirovecii as an opportunistic fungal pathogen causing severe pneumonia in immunocompromised hosts. Evidence source is OTHER as this is a review article.
PMID:27242349 SUPPORT Other
"CD4+ lymphocyte count <200 cells/µL is the primary risk factor for PJP presentation in these patients."
Identifies CD4 <200 cells/µL as the primary risk factor, anchoring the cell-mediated-immunodeficiency trigger. Evidence source is OTHER as this is a review article.
PMID:33870843 SUPPORT Other
"Risk factors for Pneumocystis jirovecii pneumonia (PJP) include HIV, organ transplant, malignancy, certain inflammatory or rheumatologic conditions, and associated therapies and conditions that result in cell-mediated immune deficiency."
Enumerates the immunocompromising risk-factor spectrum (HIV, organ transplant, malignancy, inflammatory/rheumatologic conditions and their therapies) that produces the cell-mediated-immune deficiency required for PJP, grounding the trigger node's risk-factor list. Evidence source is OTHER as this is a review article.
Alveolar Pneumonia and Respiratory Compromise
P. jirovecii attaches to the alveolar epithelium (type I pneumocytes) and produces a diffuse alveolar pneumonia with impaired gas exchange and hypoxemia; clinical signs are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue.
pulmonary alveolar type 1 cell CL:0002062 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves pulmonary alveolar type 1 cell (CL:0002062). CL:0002062 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
lung UBERON:0002048 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in lung (UBERON:0002048). UBERON:0002048 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Pneumonia Alveolar trophic attachment and host inflammatory injury directly manifest as diffuse alveolar pneumonia.
Dyspnea Diffuse alveolar exudate and impaired gas exchange produce progressive dyspnea and hypoxemia.
Fever The host alveolar and systemic inflammatory response to Pneumocystis jirovecii infection produces fever.
Show evidence (2 references)
PMID:33870843 SUPPORT Other
"Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue."
Supports the nonspecific pneumonia presentation and the requirement for direct organism detection. Evidence source is OTHER as this is a review article.
PMID:22129760 SUPPORT Human clinical
"All patients presented with respiratory failure, 10 required ventilation, two died, and six transplants failed"
Clinical transplant cohort documenting severe respiratory failure requiring mechanical ventilation in Pneumocystis jirovecii pneumonia.
Folate Synthesis (Antifolate Target)
P. jirovecii depends on de novo folate synthesis. Trimethoprim-sulfamethoxazole inhibits this pathway (sulfamethoxazole inhibits dihydropteroate synthase; trimethoprim inhibits dihydrofolate reductase), and is the first-line treatment and prophylaxis. (This antifolate target is analogous to the bacterial folate pathway but is not modeled here as conforming to the bacterial folate module, since Pneumocystis is a fungus.)
folic acid biosynthetic process GO:0046656 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves folic acid biosynthetic process (GO:0046656). GO:0046656 is a biological process from the Gene Ontology.
Show evidence (1 reference)
PMID:33870843 SUPPORT Other
"First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole"
Identifies trimethoprim-sulfamethoxazole (a folate-synthesis inhibitor) as first-line therapy and prophylaxis. Evidence source is OTHER as this is a review article.
⬡

Pathograph

Use Group by to collapse related nodes into one box. Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Pneumocystis Pneumonia Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

3
Immune 1
Pneumonia HP:0002090 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pneumonia (HP:0002090). HP:0002090 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:33870843 SUPPORT Other
"Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts."
Severe pneumonia is the defining manifestation of PJP. Evidence source is OTHER as this is a review article.
Metabolism 1
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Respiratory 1
Dyspnea HP:0002094 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dyspnea (HP:0002094). HP:0002094 is a phenotype from the Human Phenotype Ontology.
💊

Medical Actions

2
Trimethoprim-Sulfamethoxazole
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: trimethoprim CHEBI:45924 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses trimethoprim (CHEBI:45924). CHEBI:45924 is a therapeutic agent from Chemical Entities of Biological Interest. sulfamethoxazole CHEBI:9332 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses sulfamethoxazole (CHEBI:9332). CHEBI:9332 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Co-trimoxazole (trimethoprim plus sulfamethoxazole) inhibits the folate-synthesis pathway (DHFR and dihydropteroate synthase, respectively); it is the first-line treatment and prophylaxis for Pneumocystis pneumonia. Alternatives for intolerance or treatment failure include dapsone, atovaquone, pentamidine, and clindamycin-primaquine.
Mechanism Target:
INHIBITS Folate Synthesis (Antifolate Target) — Trimethoprim-sulfamethoxazole inhibits dihydrofolate reductase and dihydropteroate synthase, blocking folate synthesis the organism requires.
Show evidence (2 references)
PMID:33870843 SUPPORT Other
"First-line therapy for prophylaxis and treatment remains trimethoprim-sulfamethoxazole"
TMP-SMX is first-line therapy and prophylaxis for PJP. Evidence source is OTHER as this is a review article.
PMID:27242349 SUPPORT Other
"With data from clinical trials, trimethoprim/sulfamethoxazole (TMP/SMX) has become the primary treatment and prophylaxis of PJP in the non-HIV population, although second-line options are available."
Reinforces trimethoprim/sulfamethoxazole as primary treatment and prophylaxis of PJP in immunocompromised non-HIV hosts.
Adjunctive Corticosteroids
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: prednisone CHEBI:8382 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses prednisone (CHEBI:8382). CHEBI:8382 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
In HIV-associated PCP with hypoxemia, adjunctive corticosteroids (typically prednisone) reduce mortality.
Mechanism Target:
INHIBITS Alveolar Pneumonia and Respiratory Compromise — Adjunctive corticosteroid therapy serves as an anti-inflammatory adjunct with a mortality benefit in HIV-associated Pneumocystis pneumonia.
Show evidence (1 reference)
PMID:33870843 SUPPORT Other
"In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit."
Supports adjunctive corticosteroid use for its mortality benefit in HIV-associated Pneumocystis pneumonia.
Show evidence (1 reference)
PMID:33870843 SUPPORT Other
"In people living with HIV (PLWH), adjunctive corticosteroid use in treatment has shown a mortality benefit."
Supports adjunctive corticosteroids reducing mortality in HIV-associated PCP. Evidence source is OTHER as this is a review article.
🦠

Infectious Agent

1
Pneumocystis jirovecii
The human-restricted fungal pathogen that causes Pneumocystis pneumonia. It attaches to the alveolar epithelium and produces disease only where cell-mediated immunity is impaired; the species infecting humans is distinct from the rodent-infecting P. carinii for which the disease was once named.
Pneumocystis jirovecii NCBITaxon:42068 NCBI Taxonomy (NCBITaxon)
Show evidence (2 references)
PMID:33870843 SUPPORT Other
"Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts."
Identifies the organism as the fungal cause of pneumonia in immunocompromised hosts.
PMID:27242349 SUPPORT Other
"P jirovecii has a complicated life-cycle; it seeks to find compromised immune systems in order to replicate, causing life-threatening complications."
Supports the organism's dependence on host immune compromise for replication and disease.
↔️

Transmission

1
Airborne person-to-person acquisition
Acquisition is by the airborne route from other infected or colonized people. Nosocomial clusters among transplant recipients and genotype clustering by residence are the main lines of evidence; both are consistent with interhuman airborne spread rather than reactivation alone.
Show evidence (3 references)
PMID:22129760 SUPPORT Human clinical
"Nosocomial PJP clusters are likely due to interhuman transmission by airborne droplets to susceptible hosts."
The conclusion of a 14-case nosocomial cluster investigation, naming the airborne interhuman route.
PMID:22129760 SUPPORT Human clinical
"Contact tracing found colocalization of cases within clinic waiting areas, suggesting person-to-person transmission."
Supplies the epidemiological observation, shared clinic exposure, behind that conclusion.
PMID:16061710 SUPPORT Human clinical
"The evidence of clustering of specific genotypes with patient's postcode of residence is consistent with the hypothesis of person to person transmission of P jirovecii via the airborne route."
Independent genotyping evidence for airborne person-to-person spread, stated with the authors' own hedge.
📊

Related Datasets

3
Transcriptomic analyses of mortality in HIV-associated Pneumocystis pneumonia geo:GSE320199
Pneumocystis jirovecii pneumonia (PCP) remains a leading cause of respiratory failure and mortality in individuals with advanced HIV. While severe disease is classically attributed to hyperinflammation, the specific biological determinants driving fatal outcomes in patients remain poorly understood. To address this, we employed an integrated systems biology approach, performing transcriptomics, proteomics, and metabolomics on bronchoalveolar lavage fluid from a prospective cohort of 42 patients with HIV-associated PCP. We demonstrate that mortality is not primarily driven by uncontrolled fungal burden or isolated hyperinflammation, but by profound immunometabolic failure.
human BULK RNA SEQ n=24
Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
β-glucans are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia geo:GSE79079
β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether β-1,3 glucans are masked by surface proteins in Pneumocystis, and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, β-1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment.
mouse MICROARRAY n=11
PMID:27324243
Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
The dynamic immune cell landscape in the lungs of Pneumocystis infected mice geo:GSE157627
Pneumocystis pneumonia is an opportunistic pneumonia that has been increasing in non-HIV patients in recent years. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis, we profile the transcriptomes of mouse lungs with Pneumocystis pneumonia and from uninfected control subjects using single-cell RNA sequencing, yielding multiple populations of myeloid cells, T cells and B cells. We uncover a PCP-associated TREM2+ subpopulation of interstitial macrophages, which expands in PCP, differentiates from Ly6C+ monocytes. We also define the subsets of effector CD4+ T cells that expand after the infection of Pneumocystis.
mouse SINGLE CELL RNA SEQ n=6
PMID:33959105
Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
{ }

Source YAML

click to show 
name: Pneumocystis Pneumonia
creation_date: "2026-06-28T00:00:00Z"
description: >
  Pneumocystis pneumonia (PCP/PJP) is an opportunistic fungal pneumonia caused by
  Pneumocystis jirovecii, occurring almost exclusively in hosts with impaired
  cell-mediated immunity. Risk factors include HIV infection (classically with CD4
  counts <200 cells/µL), solid-organ transplantation, malignancy, and inflammatory
  or rheumatologic conditions and their immunosuppressive therapies. The organism
  attaches to the alveolar epithelium and produces a diffuse alveolar pneumonia
  with hypoxemia. First-line therapy and prophylaxis is
  trimethoprim-sulfamethoxazole, which targets the folate-synthesis pathway; adjunctive
  corticosteroids reduce mortality in hypoxemic HIV-associated disease.
category: Infectious Disease
parents:
- Fungal Respiratory Infection
synonyms:
- PCP
- PJP
- Pneumocystis jirovecii pneumonia
disease_term:
  preferred_term: Pneumocystis pneumonia
  term:
    id: MONDO:0005923
    label: Pneumocystis infectious disease
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:33870843
      reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts."
      explanation: Classifies Pneumocystis pneumonia as an opportunistic fungal infectious disease.
  - classification_value: RESPIRATORY
    evidence:
    - reference: PMID:33870843
      reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "Clinical signs of PJP are nonspecific and definitive diagnosis requires direct detection of the organism in lower respiratory secretions or tissue."
      explanation: Classifies Pneumocystis pneumonia as a lower respiratory tract infection requiring organism detection in lower respiratory secretions or lung tissue.
infectious_agent:
- name: Pneumocystis jirovecii
  infectious_agent_term:
    preferred_term: Pneumocystis jirovecii
    term:
      id: NCBITaxon:42068
      label: Pneumocystis jirovecii
  description: >-
    The human-restricted fungal pathogen that causes Pneumocystis pneumonia. It
    attaches to the alveolar epithelium and produces disease only where
    cell-mediated immunity is impaired; the species infecting humans is distinct
    from the rodent-infecting P. carinii for which the disease was once named.
  evidence:
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can cause severe pneumonia in immunocompromised hosts."
    explanation: Identifies the organism as the fungal cause of pneumonia in immunocompromised hosts.
  - reference: PMID:27242349
    reference_title: Pneumocystis jirovecii Pneumonia in the Non-HIV-Infected Population.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "P jirovecii has a complicated life-cycle; it seeks to find compromised immune systems in order to replicate, causing life-threatening complications."
    explanation: Supports the organism's dependence on host immune compromise for replication and disease.
transmission:
- name: Airborne person-to-person acquisition
  description: >-
    Acquisition is by the airborne route from other infected or colonized people.
    Nosocomial clusters among transplant recipients and genotype clustering by
    residence are the main lines of evidence; both are consistent with interhuman
    airborne spread rather than reactivation alone.
  evidence:
  - reference: PMID:22129760
    reference_title: "Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Nosocomial PJP clusters are likely due to interhuman transmission by airborne droplets to susceptible hosts."
    explanation: The conclusion of a 14-case nosocomial cluster investigation, naming the airborne interhuman route.
  - reference: PMID:22129760
    reference_title: "Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Contact tracing found colocalization of cases within clinic waiting areas, suggesting person-to-person transmission."
    explanation: Supplies the epidemiological observation, shared clinic exposure, behind that conclusion.
  - reference: PMID:16061710
    reference_title: Genotypic variation in Pneumocystis jirovecii isolates in Britain.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The evidence of clustering of specific genotypes with patient's postcode of residence is consistent with the hypothesis of person to person transmission of P jirovecii via the airborne route."
    explanation: Independent genotyping evidence for airborne person-to-person spread, stated with the authors' own hedge.
pathophysiology:
- name: Opportunistic Infection in Cell-Mediated Immunodeficiency
  role: trigger
  description: >
    Pneumocystis jirovecii is an opportunistic fungal pathogen that causes severe
    pneumonia in immunocompromised hosts. Disease requires impaired cell-mediated
    immunity — HIV (where CD4+ T-cell depletion <200 cells/µL is the classic
    marker), organ transplantation, malignancy, and inflammatory/rheumatologic
    conditions and their immunosuppressive therapies (which impair broader
    cell-mediated immunity beyond CD4 count alone) — permitting uncontrolled
    alveolar replication.
  cell_types:
  - preferred_term: CD4-positive, alpha-beta T cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  biological_processes:
  - preferred_term: symbiont entry into host cell
    term:
      id: GO:0046718
      label: symbiont entry into host cell
  evidence:
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can
      cause severe pneumonia in immunocompromised hosts.
    explanation: >-
      Establishes P. jirovecii as an opportunistic fungal pathogen causing severe
      pneumonia in immunocompromised hosts. Evidence source is OTHER as this is a
      review article.
  - reference: PMID:27242349
    reference_title: Pneumocystis jirovecii Pneumonia in the Non-HIV-Infected Population.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      CD4+ lymphocyte count <200 cells/µL is the primary risk factor for PJP
      presentation in these patients.
    explanation: >-
      Identifies CD4 <200 cells/µL as the primary risk factor, anchoring the
      cell-mediated-immunodeficiency trigger. Evidence source is OTHER as this is a
      review article.
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Risk factors for Pneumocystis jirovecii pneumonia (PJP) include HIV, organ
      transplant, malignancy, certain inflammatory or rheumatologic conditions,
      and associated therapies and conditions that result in cell-mediated immune
      deficiency.
    explanation: >-
      Enumerates the immunocompromising risk-factor spectrum (HIV, organ
      transplant, malignancy, inflammatory/rheumatologic conditions and their
      therapies) that produces the cell-mediated-immune deficiency required for
      PJP, grounding the trigger node's risk-factor list. Evidence source is OTHER
      as this is a review article.
  downstream:
  - target: Alveolar Pneumonia and Respiratory Compromise
    description: >-
      Uncontrolled alveolar replication produces a diffuse pneumonia with impaired
      gas exchange.

- name: Alveolar Pneumonia and Respiratory Compromise
  role: consequence
  description: >
    P. jirovecii attaches to the alveolar epithelium (type I pneumocytes) and
    produces a diffuse alveolar pneumonia with impaired gas exchange and hypoxemia;
    clinical signs are nonspecific and definitive diagnosis requires direct
    detection of the organism in lower respiratory secretions or tissue.
  cell_types:
  - preferred_term: pulmonary alveolar type 1 cell
    term:
      id: CL:0002062
      label: pulmonary alveolar type 1 cell
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
    modifier: INCREASED
  locations:
  - preferred_term: lung
    term:
      id: UBERON:0002048
      label: lung
  evidence:
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Clinical signs of PJP are nonspecific and definitive diagnosis requires
      direct detection of the organism in lower respiratory secretions or tissue.
    explanation: >-
      Supports the nonspecific pneumonia presentation and the requirement for direct
      organism detection. Evidence source is OTHER as this is a review article.
  - reference: PMID:22129760
    reference_title: "Nosocomial Pneumocystis jirovecii pneumonia: lessons from a cluster in kidney transplant recipients."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      All patients presented with respiratory failure, 10 required ventilation,
      two died, and six transplants failed
    explanation: >-
      Clinical transplant cohort documenting severe respiratory failure requiring
      mechanical ventilation in Pneumocystis jirovecii pneumonia.
  downstream:
  - target: Pneumonia
    description: >-
      Alveolar trophic attachment and host inflammatory injury directly manifest
      as diffuse alveolar pneumonia.
  - target: Dyspnea
    description: >-
      Diffuse alveolar exudate and impaired gas exchange produce progressive
      dyspnea and hypoxemia.
  - target: Fever
    description: >-
      The host alveolar and systemic inflammatory response to Pneumocystis
      jirovecii infection produces fever.

- name: Folate Synthesis (Antifolate Target)
  role: therapeutic_vulnerability
  description: >
    P. jirovecii depends on de novo folate synthesis. Trimethoprim-sulfamethoxazole
    inhibits this pathway (sulfamethoxazole inhibits dihydropteroate synthase;
    trimethoprim inhibits dihydrofolate reductase), and is the first-line treatment
    and prophylaxis. (This antifolate target is analogous to the bacterial folate
    pathway but is not modeled here as conforming to the bacterial folate module,
    since Pneumocystis is a fungus.)
  biological_processes:
  - preferred_term: folic acid biosynthetic process
    term:
      id: GO:0046656
      label: folic acid biosynthetic process
  evidence:
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      First-line therapy for prophylaxis and treatment remains
      trimethoprim-sulfamethoxazole
    explanation: >-
      Identifies trimethoprim-sulfamethoxazole (a folate-synthesis inhibitor) as
      first-line therapy and prophylaxis. Evidence source is OTHER as this is a
      review article.
  downstream: []
phenotypes:
- category: Respiratory
  name: Pneumonia
  description: >
    Diffuse alveolar pneumonia is the defining manifestation.
  phenotype_term:
    preferred_term: Pneumonia
    term:
      id: HP:0002090
      label: Pneumonia
  evidence:
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Pneumocystis jirovecii (PJ) is an opportunistic fungal pathogen that can
      cause severe pneumonia in immunocompromised hosts.
    explanation: >-
      Severe pneumonia is the defining manifestation of PJP. Evidence source is
      OTHER as this is a review article.
- category: Respiratory
  name: Dyspnea
  description: >
    Progressive dyspnea with hypoxemia is characteristic of PCP.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
- category: Constitutional
  name: Fever
  description: >
    Fever commonly accompanies Pneumocystis pneumonia.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
treatments:
- name: Trimethoprim-Sulfamethoxazole
  description: >
    Co-trimoxazole (trimethoprim plus sulfamethoxazole) inhibits the folate-synthesis
    pathway (DHFR and dihydropteroate synthase, respectively); it is the first-line
    treatment and prophylaxis for Pneumocystis pneumonia. Alternatives for
    intolerance or treatment failure include dapsone, atovaquone, pentamidine, and
    clindamycin-primaquine.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: trimethoprim
      term:
        id: CHEBI:45924
        label: trimethoprim
    - preferred_term: sulfamethoxazole
      term:
        id: CHEBI:9332
        label: sulfamethoxazole
  target_mechanisms:
  - target: Folate Synthesis (Antifolate Target)
    treatment_effect: INHIBITS
    description: >-
      Trimethoprim-sulfamethoxazole inhibits dihydrofolate reductase and
      dihydropteroate synthase, blocking folate synthesis the organism requires.
  evidence:
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      First-line therapy for prophylaxis and treatment remains
      trimethoprim-sulfamethoxazole
    explanation: >-
      TMP-SMX is first-line therapy and prophylaxis for PJP. Evidence source is
      OTHER as this is a review article.
  - reference: PMID:27242349
    reference_title: Pneumocystis jirovecii Pneumonia in the Non-HIV-Infected Population.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      With data from clinical trials, trimethoprim/sulfamethoxazole (TMP/SMX) has
      become the primary treatment and prophylaxis of PJP in the non-HIV
      population, although second-line options are available.
    explanation: >-
      Reinforces trimethoprim/sulfamethoxazole as primary treatment and prophylaxis
      of PJP in immunocompromised non-HIV hosts.
- name: Adjunctive Corticosteroids
  description: >
    In HIV-associated PCP with hypoxemia, adjunctive corticosteroids (typically
    prednisone) reduce mortality.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: prednisone
      term:
        id: CHEBI:8382
        label: prednisone
  target_mechanisms:
  - target: Alveolar Pneumonia and Respiratory Compromise
    treatment_effect: INHIBITS
    description: >-
      Adjunctive corticosteroid therapy serves as an anti-inflammatory adjunct
      with a mortality benefit in HIV-associated Pneumocystis pneumonia.
    evidence:
    - reference: PMID:33870843
      reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        In people living with HIV (PLWH), adjunctive corticosteroid use in treatment
        has shown a mortality benefit.
      explanation: >-
        Supports adjunctive corticosteroid use for its mortality benefit in
        HIV-associated Pneumocystis pneumonia.
  evidence:
  - reference: PMID:33870843
    reference_title: "Pneumocystis jirovecii: a review with a focus on prevention and treatment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      In people living with HIV (PLWH), adjunctive corticosteroid use in treatment
      has shown a mortality benefit.
    explanation: >-
      Supports adjunctive corticosteroids reducing mortality in HIV-associated PCP.
      Evidence source is OTHER as this is a review article.
notes: >-
  Created as part of the Respiratory Infections project (opportunistic fungal
  pneumonia). Deliberately NOT conformed to the bacterial_folate_synthesis_inhibition
  module: although TMP-SMX targets the same folate enzymes, that module's selectivity
  rationale is prokaryote-specific and Pneumocystis is a fungus. disease_term uses
  MONDO:0005923 (Pneumocystis infectious disease) with a more specific preferred_term
  because MONDO lacks a dedicated "Pneumocystis pneumonia" term.
datasets:
- accession: geo:GSE320199
  title: Transcriptomic analyses of mortality in HIV-associated Pneumocystis pneumonia
  description: Pneumocystis jirovecii pneumonia (PCP) remains a leading cause of respiratory failure and mortality in individuals with advanced HIV. While severe disease is classically attributed to hyperinflammation, the specific biological determinants driving fatal outcomes in patients remain poorly understood. To address this, we employed an integrated systems biology approach, performing transcriptomics, proteomics, and metabolomics on bronchoalveolar lavage fluid from a prospective cohort of 42 patients with HIV-associated PCP. We demonstrate that mortality is not primarily driven by uncontrolled fungal burden or isolated hyperinflammation, but by profound immunometabolic failure.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 24
  notes: Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE79079
  title: β-glucans are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia
  description: β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether β-1,3 glucans are masked by surface proteins in Pneumocystis, and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, β-1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: MICROARRAY
  sample_count: 11
  publication: PMID:27324243
  notes: Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE157627
  title: The dynamic immune cell landscape in the lungs of Pneumocystis infected mice
  description: Pneumocystis pneumonia is an opportunistic pneumonia that has been increasing in non-HIV patients in recent years. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis, we profile the transcriptomes of mouse lungs with Pneumocystis pneumonia and from uninfected control subjects using single-cell RNA sequencing, yielding multiple populations of myeloid cells, T cells and B cells. We uncover a PCP-associated TREM2+ subpopulation of interstitial macrophages, which expands in PCP, differentiates from Ly6C+ monocytes. We also define the subsets of effector CD4+ T cells that expand after the infection of Pneumocystis.
  organism:
    preferred_term: mouse
    term:
      id: NCBITaxon:10090
      label: Mus musculus
  data_type: SINGLE_CELL_RNA_SEQ
  sample_count: 6
  publication: PMID:33959105
  notes: Identified by GEO DataSets index search for Pneumocystis Pneumonia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.