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

Frontiers in immunology

Authors: Kevin Baßler, Wataru Fujii, Theodore S Kapellos, Erika Dudkin, Nico Reusch, Ari Horne, Benedikt Reiz, Malte D Luecken, Collins Osei-Sarpong, Stefanie Warnat-Herresthal, Lorenzo Bonaguro, Jonas Schulte-Schrepping, Allon Wagner, Patrick Günther, Carmen Pizarro, Tina Schreiber, Rainer Knoll, Lisa Holsten, Charlotte Kröger, Elena De Domenico, Matthias Becker, Kristian Händler, Christian T Wohnhaas, Florian Baumgartner, Meike Köhler, Heidi Theis, Michael Kraut, Marc H Wadsworth, Travis K Hughes, Humberto J Ferreira, Emily Hinkley, Ines H Kaltheuner, Matthias Geyer, Christoph Thiele, Alex K Shalek, Andreas Feißt, Daniel Thomas, Henning Dickten, Marc Beyer, Patrick Baum, Nir Yosef, Anna C Aschenbrenner, Thomas Ulas, Jan Hasenauer, Fabian J Theis, Dirk Skowasch, Joachim L Schultze

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.

Copyright © 2022 Baßler, Fujii, Kapellos, Dudkin, Reusch, Horne, Reiz, Luecken, Osei-Sarpong, Warnat-Herresthal, Bonaguro, Schulte-Schrepping, Wagner, Günther, Pizarro, Schreiber, Knoll, Holsten, Kröger, De Domenico, Becker, Händler, Wohnhaas, Baumgartner, Köhler, Theis, Kraut, Wadsworth, Hughes, Ferreira, Hinkley, Kaltheuner, Geyer, Thiele, Shalek, Feißt, Thomas, Dickten, Beyer, Baum, Yosef, Aschenbrenner, Ulas, Hasenauer, Theis, Skowasch and Schultze.

PMID: 35979364

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