Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation

Bassler K, Fujii W, Kapellos TS, Dudkin E, Reusch N, Horne A, Reiz B, Luecken MD, Osei-Sarpong C, Warnat-Herresthal S, Bonaguro L, Schulte-Schrepping J, Wagner A, Guenther P, Pizarro C, Schreiber T, Knoll R, Holsten L, Kroeger C, De Domenico E, Becker M, Haendler K, Wohnhaas CT, Baumgartner F, Koehler M, Theis H, Kraut M, Wadsworth MH, Hughes TK, Ferreira HJ, Hinkley E, Kaltheuner IH, Geyer M, Thiele C, Shalek AK, Feisst A, Thomas D, Dickten H, Beyer M, Baum P, Yosef N, Aschenbrenner AC, Ulas T, Hasenauer J, Theis FJ, Skowasch D, Schultze JL (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 13

Article Number: 917232

DOI: 10.3389/fimmu.2022.917232

Abstract

Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-β1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Comma Soft AG DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) University of California, Berkeley US United States (USA) (US) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) NL Netherlands (NL) Technische Universität München (TUM) DE Germany (DE) Massachusetts Institute of Technology (MIT) US United States (USA) (US) Universitätsklinikum Bonn DE Germany (DE) Boehringer Ingelheim Pharma GmbH & Co. KG DE Germany (DE)

How to cite

APA:

Bassler, K., Fujii, W., Kapellos, T.S., Dudkin, E., Reusch, N., Horne, A.,... Schultze, J.L. (2022). Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.917232

MLA:

Bassler, Kevin, et al. "Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation." Frontiers in Immunology 13 (2022).

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