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

被引：22

作者：

Bassler, Kevin ^{[1
]}

Fujii, Wataru ^{[1
]}

Kapellos, Theodore S. ^{[1
]}

Dudkin, Erika ^{[2
]}

Reusch, Nico ^{[1
]}

Horne, Ari ^{[1
]}

Reiz, Benedikt ^{[3
]}

Luecken, Malte D. ^{[4
]}

Osei-Sarpong, Collins ^{[5
,6
]}

Warnat-Herresthal, Stefanie ^{[1
]}

Bonaguro, Lorenzo ^{[1
,6
,7
,8
]}

Schulte-Schrepping, Jonas ^{[1
]}

Wagner, Allon ^{[9
,10
]}

Guenther, Patrick ^{[6
,7
]}

Pizarro, Carmen ^{[11
]}

Schreiber, Tina ^{[11
]}

Knoll, Rainer ^{[1
,6
,7
,12
]}

Holsten, Lisa ^{[1
]}

Kroeger, Charlotte ^{[1
,12
]}

De Domenico, Elena ^{[6
,7
,8
]}

Becker, Matthias ^{[6
,7
,8
]}

Haendler, Kristian ^{[6
,7
,8
]}

Wohnhaas, Christian T. ^{[13
]}

Baumgartner, Florian ^{[3
]}

Koehler, Meike ^{[3
]}

Theis, Heidi ^{[6
,7
,8
]}

Kraut, Michael ^{[6
,7
,8
]}

Wadsworth, Marc H. ^{[14
,15
,16
,17
]}

Hughes, Travis K. ^{[18
]}

Ferreira, Humberto J. ^{[6
,7
]}

Hinkley, Emily ^{[6
,7
,8
]}

Kaltheuner, Ines H. ^{[18
]}

Geyer, Matthias ^{[19
]}

Thiele, Christoph ^{[20
]}

Shalek, Alex K. ^{[14
,15
,16
,17
]}

Feisst, Andreas ^{[20
]}

Thomas, Daniel ^{[20
]}

Dickten, Henning ^{[3
]}

Beyer, Marc ^{[5
,6
,7
,8
]}

Baum, Patrick ^{[21
]}

Yosef, Nir ^{[9
,10
,16
,22
]}

Aschenbrenner, Anna C. ^{[12
,16
]}

Ulas, Thomas ^{[1
,6
,7
,8
]}

Hasenauer, Jan ^{[2
,4
]}

Theis, Fabian J. ^{[4
]}

Skowasch, Dirk ^{[11
]}

Schultze, Joachim L. ^{[1
,6
,7
,8
]}

机构：

[1] Univ Bonn, Life & Med Sci LIMES Inst, Genom & Immunoregulat, Bonn, Germany

[2] Univ Bonn, Life & Med Sci LIMES Inst, Computat Life Sci, Neuherberg, Germany

[3] Comma Soft AG, Bonn, Germany

[4] Inst Computat Biol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany

[5] German Ctr Neurodegenerat Dis, Immunogen & Neurodegenerat, Bonn, Germany

[6] German Ctr Neurodegenerat Dis DZNE, PRECISE Platform Single Cell Genom & Epigen, Bonn, Germany

[7] Univ Bonn, Bonn, Germany

[8] German Ctr Neurodegenerat Dis DZNE, Syst Med, Bonn, Germany

[9] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA USA

[10] Radboud Univ Nijmegen Med Ctr, Dept Internal Med, Nijmegen, CA, Netherlands

[11] Radboud Univ Nijmegen Med Ctr, Radboud Ctr Infect Dis RCI, Sect Pneumol, Bonn, Germany

[12] Tech Univ Munich, Sch Life Sci Weihenstephan, Bonn, Germany

[13] Tech Univ Munich, Dept Math, Munich, Germany

[14] Aimed analyt, Inst Med Engn & Sci, Dept Chem, Cambridge, MA USA

[15] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Inflammat & Immunol, Kyoto, MA, Japan

[16] Broad Inst MIT & Harvard, Cambridge, MA USA

[17] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA

[18] Univ Bonn, Univ Hosp, Inst Struct Biol, Bonn, Germany

[19] Univ Bonn, Life & Med Sci LIMES Inst, Biochem & Cell Biol Lipids, Bonn, Germany

[20] Univ Clin Radiol, Univ Hosp Bonn, Bonn, Germany

[21] Boehringer Ingelheim Pharm GmbH & Co KG, Translat Med & Clin Pharmacol, Biberach, Germany

[22] Chan Zuckerberg Biohub, San Francisco, CA USA

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

关键词：

chronic obstructive pulmonary disease; bronchoalveolar lavage; blood; macrophage; monocyte; impaired immune activation; TGF-beta; 1; OBSTRUCTIVE PULMONARY-DISEASE; CIGARETTE-SMOKE; R PACKAGE; EXPRESSION; PATHWAY; CELLS; RECONSTRUCTION; BIOCONDUCTOR; PATHOGENESIS; METABOLISM;

D O I：

10.3389/fimmu.2022.917232

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-beta 1 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.

引用

页数：31

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