Human alveolar macrophages display marked hypo-responsiveness to IFN-γ in both proteomic and gene expression analysis.

Autor: Thiel BA; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America., Lundberg KC; Department of Nutrition, Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America., Schlatzer D; Department of Nutrition, Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America., Jarvela J; Division of Pulmonary, Critical Care, and Sleep Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, United States of America., Li Q; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America., Shaw R; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America., Reba SM; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America., Fletcher S; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America., Beckloff SE; Biobot Analytics, Cambridge, Massachusetts, United States of America., Chance MR; Department of Nutrition, Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America., Boom WH; Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America., Silver RF; Division of Pulmonary, Critical Care, and Sleep Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, United States of America.; Division of Pulmonary, Critical Care, and Sleep Medicine, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America., Bebek G; Department of Nutrition, Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Feb 01; Vol. 19 (2), pp. e0295312. Date of Electronic Publication: 2024 Feb 01 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0295312
Abstrakt: Alveolar macrophages (AM) perform a primary defense mechanism in the lung through phagocytosis of inhaled particles and microorganisms. AM are known to be relatively immunosuppressive consistent with the aim to limit alveolar inflammation and maintain effective gas exchange in the face of these constant challenges. How AM respond to T cell derived cytokine signals, which are critical to the defense against inhaled pathogens, is less well understood. For example, successful containment of Mycobacterium tuberculosis (Mtb) in lung macrophages is highly dependent on IFN-γ secreted by Th-1 lymphocytes, however, the proteomic IFN-γ response profile in AM remains mostly unknown. In this study, we measured IFN-γ induced protein abundance changes in human AM and autologous blood monocytes (MN). AM cells were activated by IFN-γ stimulation resulting in STAT1 phosphorylation and production of MIG/CXCL9 chemokine. However, the global proteomic response to IFN-γ in AM was dramatically limited in comparison to that of MN (9 AM vs 89 MN differentially abundant proteins). AM hypo-responsiveness was not explained by reduced JAK-STAT1 signaling nor increased SOCS1 expression. These findings suggest that AM have a tightly regulated response to IFN-γ which may prevent excessive pulmonary inflammation but may also provide a niche for the initial survival and growth of Mtb and other intracellular pathogens in the lung.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Thiel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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