RGD Reference Report - The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum. - Rat Genome Database

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The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum.

Authors: Lázár-Molnár, Eszter  Gácser, Attila  Freeman, Gordon J  Almo, Steven C  Nathenson, Stanley G  Nosanchuk, Joshua D 
Citation: Lázár-Molnár E, etal., Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2658-63. doi: 10.1073/pnas.0711918105. Epub 2008 Feb 11.
RGD ID: 40822806
Pubmed: PMID:18268348   (View Abstract at PubMed)
PMCID: PMC2268192   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0711918105   (Journal Full-text)

The PD-1 costimulatory receptor inhibits T cell receptor signaling upon interacting with its ligands PD-L1 and PD-L2. The PD-1/PD-L pathway is critical in maintaining self-tolerance. In this study, we examined the role of PD-1 in a mouse model of acute infection with Histoplasma capsulatum, a major human pathogenic fungus. In a lethal model of histoplasmosis, all PD-1-deficient mice survived infection, whereas the wild-type mice died with disseminated disease. PD-L expression on macrophages and splenocytes was up-regulated during infection, and macrophages from infected mice inhibited in vitro T cell activation. Of interest, antibody blocking of PD-1 significantly increased survival of lethally infected wild-type mice. Thus, our studies extend the role of the PD-1/PD-L pathway in regulating antimicrobial immunity to fungal pathogens. The results show that the PD-1/PD-L pathway has a key role in the regulation of antifungal immunity, and suggest that manipulation of this pathway represents a strategy of immunotherapy for histoplasmosis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
histoplasmosis  ISOCd274 (Mus musculus)40822806; 40822806protein:increased expression:macrophage more ...RGD 
histoplasmosis  IEP 40822806protein:increased expression:macrophage more ...RGD 
histoplasmosis treatmentISOPdcd1 (Mus musculus)40822806; 40822806 RGD 
histoplasmosis  ISOPdcd1lg2 (Mus musculus)40822806; 40822806protein:increased expression:macrophage and dendritic cellRGD 
histoplasmosis treatmentIMP 40822806 RGD 
histoplasmosis  IEP 40822806protein:increased expression:macrophage and dendritic cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd274  (CD274 molecule)
Pdcd1  (programmed cell death 1)
Pdcd1lg2  (programmed cell death 1 ligand 2)

Genes (Mus musculus)
Cd274  (CD274 antigen)
Pdcd1  (programmed cell death 1)
Pdcd1lg2  (programmed cell death 1 ligand 2)

Genes (Homo sapiens)
CD274  (CD274 molecule)
PDCD1  (programmed cell death 1)
PDCD1LG2  (programmed cell death 1 ligand 2)


Additional Information