ArticleInfection and immunity2015
Neither classical nor alternative macrophage activation is required for Pneumocystis clearance during immune reconstitution inflammatory syndrome.
Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Modulation of host lung immunity in Pneumocystis pneumonia: a review of current concepts and future prospects for novel adjunctive immune-based therapies.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Immune responses of different hosts toEuropean respiratory review : an official journal of the European Respiratory Society · 2025Review
- T-cell subsets inClinical & translational immunology · 2025Review
- IFN-γ Limits Immunopathogenesis but Delays Fungal Clearance during Pneumocystis Pneumonia.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- The Dual Benefit of Sulfasalazine on Pneumocystis Pneumonia-Related Immunopathogenesis and Antifungal Host Defense Does Not Require IL-4Rα-Dependent Macrophage Polarization.Infection and immunity · 2023Article
- The Role of Macrophages and Alveolar Epithelial Cells in the Development of ARDS.Inflammation · 2023Review
- Bias of the Immune Response toJournal of fungi (Basel, Switzerland) · 2021Article
- Immune Response inJournal of fungi (Basel, Switzerland) · 2021Review
- Immune reconstitution inflammatory syndrome associated withThe Journal of international medical research · 2020Article
- Combination Immunotherapy with Passive Antibody and Sulfasalazine Accelerates Fungal Clearance and Promotes the Resolution ofInfection and immunity · 2020Article
- Understanding mechanisms underlying the pathology of immune reconstitution inflammatory syndrome (IRIS) by using animal models.Current clinical microbiology reports · 2018Article
- Intrinsic Programming of Alveolar Macrophages for Protective Antifungal Innate Immunity AgainstFrontiers in immunology · 2018Article
- Pneumocystis infection alters the activation state of pulmonary macrophages.Immunobiology · 2017Article
- Immune reconstitution inflammatory syndrome associated with pulmonary pathogens.European respiratory review : an official journal of the European Respiratory Society · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4(+) T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2(-/-) mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2(-/-) mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-γR(-/-) nor RAG/IL-4Rα(-/-) mice displayed impaired Pneumocystis clearance. However, RAG/IFN-γR(-/-) mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα(-/-) mice. RAG/IFN-γR(-/-) mice had elevated numbers of lung CD4(+) T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8(+) T suppressor cells. Impaired lung CD8(+) T cell responses in RAG/IFN-γR(-/-) mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8(+) T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS.
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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.