ArticleProceedings of the National Academy of Sciences of the United States of America2008
The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed, 113 citations in OpenAlex.
- Exhausted T cell phenotypes in disseminated coccidioidomycosis.JCI insight · 2026Article
- Mycobacterium avium infection induced PD-L1 overexpression in macrophages: a potential involvement with immune escape.Cell death & disease · 2026Article
- Emergence, function, and therapeutic strategies to target the PD-1/PD-L1 immune checkpoint during pathogenic fungal infections.Virulence · 2025Review
- Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.Acta pharmaceutica Sinica. B · 2025Review
- Immunoengineering: An Emerging Field in Infectious Diseases.The Journal of infectious diseases · 2025Review
- A narrative review of the controversy on the risk of mycobacterial infections with immune checkpoint inhibitor use: does Goldilocks have the answer?Journal of thoracic disease · 2024Review
- Circulatory Inflammatory Proteins as Early Diagnostic Biomarkers for Invasive Aspergillosis in Patients with Hematologic Malignancies-an Exploratory Study.Mycopathologia · 2024Article
- Blocking the CTLA-4 and PD-1 pathways during pulmonary paracoccidioidomycosis improves immunity, reduces disease severity, and increases the survival of infected mice.Frontiers in immunology · 2024Article
- New Immunological Markers in Chromoblastomycosis-The Importance of PD-1 and PD-L1 Molecules in Human Infection.Journal of fungi (Basel, Switzerland) · 2023Article
- New anticancer therapeutics impact fungal pathobiology, infection dynamics, and outcome.PLoS pathogens · 2023Article
- PD-1 receptor outside the main paradigm: tumour-intrinsic role and clinical implications for checkpoint blockade.British journal of cancer · 2023Review
- Unmasking a fungal fire.PLoS pathogens · 2023Article
- They shall not grow mold: Soldiers of innate and adaptive immunity to fungi.Seminars in immunology · 2023Review
- Role of regulation of PD-1 and PD-L1 expression in sepsis.Frontiers in immunology · 2023Review
- Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies.International journal of molecular sciences · 2022Review
- Mitogen-activated protein kinase phosphatase-1 controls PD-L1 expression by regulating type I interferon during systemic Escherichia coli infection.The Journal of biological chemistry · 2022Article
- [Pneumocystis jirovecii Pneumonia in Patients with Lung Cancer: A Review].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
- Case Report: Immune Checkpoint Blockade Plus Interferon-Γ Add-On Antifungal Therapy in the Treatment of Refractory Covid-Associated Pulmonary Aspergillosis and Cerebral Mucormycosis.Frontiers in immunology · 2022Article
- Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions.Frontiers in immunology · 2022Review
- Case Report: New Onset Lymphadenopathy After Immune Checkpoint Inhibitor Therapy Presents a Clinicopathological and Radiological Challenge.Frontiers in oncology · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.