Dataset Information

Alveolar Macrophages Inherently Express Programmed Death-1 Ligand 1 for Optimal Protective Immunity and Tolerance.

ABSTRACT: Macrophages play a central role in lung physiology and pathology. In this study, we show in mice that alveolar macrophages (AMs), unlike other macrophage types (interstitial, peritoneal, and splenic macrophages), constitutively express programmed death-1 ligand 1 (PD-L1), thereby possessing a superior phagocytic ability and the capacity to repress CTLs by cis- and trans-interacting with CD80 and programmed death-1 (PD-1), respectively. This extraordinary ability of AMs assures optimal protective immunity and tolerance within the lung. These findings uncover a unique characteristic of AMs and an innate immune function of PD-L1 and CD80 and therefore help in the understanding of lung physiology, diseases, and PD-L1/PD-1-based immunotherapy.

SUBMITTER: Sun F

PROVIDER: S-EPMC8674373 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Alveolar Macrophages Inherently Express Programmed Death-1 Ligand 1 for Optimal Protective Immunity and Tolerance.

Sun Fan F Li Liwen L Xiao Yadong Y Gregory Alyssa D AD Shapiro Steven D SD Xiao Gutian G Qu Zhaoxia Z

Journal of immunology (Baltimore, Md. : 1950) 20210616 1

Macrophages play a central role in lung physiology and pathology. In this study, we show in mice that alveolar macrophages (AMs), unlike other macrophage types (interstitial, peritoneal, and splenic macrophages), constitutively express programmed death-1 ligand 1 (PD-L1), thereby possessing a superior phagocytic ability and the capacity to repress CTLs by <i>cis</i>- and <i>trans</i>-interacting with CD80 and programmed death-1 (PD-1), respectively. This extraordinary ability of AMs assures opti ...[more]

PMID: 34135059

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Project description:Invasive fungal infections, including Pneumocystis Pneumonia (PcP), remain frequent life-threatening conditions of patients with adaptive immune defects. While innate immunity helps control pathogen growth early during infection, it is typically not sufficient for complete protection against Pneumocystis and other human fungal pathogens. Alveolar macrophages (AM) possess pattern recognition molecules capable of recognizing antigenic and structural determinants of Pneumocystis. However, this pathogen effectively evades innate immunity to infect both immunocompetent and immunosuppressed hosts, albeit with differing outcomes. During our studies of mouse models of PcP, the FVB/N strain was identified as unique because of its ability to mount a protective innate immune response against Pneumocystis infection. In contrast to other immunocompetent strains, which become transiently infected prior to the onset of adaptive immunity, FVB/N mice rapidly eradicated Pneumocystis before an adaptive immune response was triggered. Furthermore, FVB/N mice remained highly resistant to infection even in the absence of functional T cells. The effector mechanism of innate protection required the action of functional alveolar macrophages, and the adoptive transfer of resistant FVB/N AMs, but not susceptible CB.17 AMs, conferred protection to immunodeficient mice. Macrophage IFNγ receptor signaling was not required for innate resistance, and FVB/N macrophages were found to display markers of alternative activation. IFNγ reprogrammed resistant FVB/N macrophages to a permissive M1 biased phenotype through a mechanism that required direct activation of the macrophage IFNγR. These results demonstrate that appropriately programmed macrophages provide protective innate immunity against this opportunistic fungal pathogen, and suggest that modulating macrophage function may represent a feasible therapeutic strategy to enhance antifungal host defense. The identification of resistant and susceptible macrophages provides a novel platform to study not only the mechanisms of macrophage-mediated antifungal defense, but also the mechanisms by which Pneumocystis evades innate immunity.

Dataset Information

Alveolar Macrophages Inherently Express Programmed Death-1 Ligand 1 for Optimal Protective Immunity and Tolerance.

Publications

Alveolar Macrophages Inherently Express Programmed Death-1 Ligand 1 for Optimal Protective Immunity and Tolerance.

Similar Datasets

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