Frontiers in Immunology (Jul 2022)

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

  • 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,
  • Lorenzo Bonaguro,
  • Lorenzo Bonaguro,
  • Jonas Schulte-Schrepping,
  • Allon Wagner,
  • Allon Wagner,
  • Patrick Günther,
  • Carmen Pizarro,
  • Tina Schreiber,
  • Rainer Knoll,
  • Rainer Knoll,
  • Rainer Knoll,
  • Lisa Holsten,
  • Charlotte Kröger,
  • Charlotte Kröger,
  • Elena De Domenico,
  • Elena De Domenico,
  • Matthias Becker,
  • Matthias Becker,
  • Kristian Händler,
  • Kristian Händler,
  • Christian T. Wohnhaas,
  • Florian Baumgartner,
  • Meike Köhler,
  • Heidi Theis,
  • Heidi Theis,
  • Michael Kraut,
  • Michael Kraut,
  • Marc H. Wadsworth,
  • Marc H. Wadsworth,
  • Travis K. Hughes,
  • Humberto J. Ferreira,
  • Emily Hinkley,
  • Emily Hinkley,
  • Ines H. Kaltheuner,
  • Matthias Geyer,
  • Christoph Thiele,
  • Alex K. Shalek,
  • Alex K. Shalek,
  • Andreas Feißt,
  • Daniel Thomas,
  • Henning Dickten,
  • Marc Beyer,
  • Marc Beyer,
  • Marc Beyer,
  • Patrick Baum,
  • Nir Yosef,
  • Nir Yosef,
  • Nir Yosef,
  • Nir Yosef,
  • Anna C. Aschenbrenner,
  • Anna C. Aschenbrenner,
  • Anna C. Aschenbrenner,
  • Thomas Ulas,
  • Thomas Ulas,
  • Thomas Ulas,
  • Jan Hasenauer,
  • Jan Hasenauer,
  • Fabian J. Theis,
  • Fabian J. Theis,
  • Dirk Skowasch,
  • Joachim L. Schultze,
  • Joachim L. Schultze,
  • Joachim L. Schultze

DOI
https://doi.org/10.3389/fimmu.2022.917232
Journal volume & issue
Vol. 13

Abstract

Read online

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.

Keywords