AUTHOR=Baßler Kevin , Fujii Wataru , Kapellos Theodore S. , Dudkin Erika , Reusch Nico , Horne Ari , Reiz Benedikt , Luecken Malte D. , Osei-Sarpong Collins , Warnat-Herresthal Stefanie , Bonaguro Lorenzo , Schulte-Schrepping Jonas , Wagner Allon , Günther Patrick , Pizarro Carmen , Schreiber Tina , Knoll Rainer , Holsten Lisa , Kröger Charlotte , De Domenico Elena , Becker Matthias , Händler Kristian , Wohnhaas Christian T. , Baumgartner Florian , Köhler Meike , Theis Heidi , Kraut Michael , Wadsworth Marc H. , Hughes Travis K. , Ferreira Humberto J. , Hinkley Emily , Kaltheuner Ines H. , Geyer Matthias , Thiele Christoph , Shalek Alex K. , Feißt Andreas , Thomas Daniel , Dickten Henning , Beyer Marc , Baum Patrick , Yosef Nir , Aschenbrenner Anna C. , Ulas Thomas , Hasenauer Jan , Theis Fabian J. , Skowasch Dirk , Schultze Joachim L. TITLE=Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.917232 DOI=10.3389/fimmu.2022.917232 ISSN=1664-3224 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.