CD8+ T cells induce cachexia during chronic viral infection

被引：65

作者：

Baazim, Hatoon ^{[1
]}

Schweiger, Martina ^{[2
]}

Moschinger, Michael ^{[1
]}

Xu, Haifeng ^{[3
]}

Scherer, Thomas ^{[4
]}

Popa, Alexandra ^{[1
]}

Gallage, Suchira ^{[5
]}

Ali, Adnan ^{[1
]}

Khamina, Kseniya ^{[1
]}

Kosack, Lindsay ^{[1
]}

Vilagos, Bojan ^{[1
]}

Smyth, Mark ^{[1
]}

Lercher, Alexander ^{[1
]}

Friske, Joachim ^{[6
]}

Merkler, Doron ^{[7
]}

Aderem, Alan ^{[8
]}

Helbich, Thomas H. ^{[6
]}

Heikenwaelder, Mathias ^{[5
]}

Lang, Philipp A. ^{[3
]}

Zechner, Rudolf ^{[2
]}

Bergthaler, Andreas ^{[1
]}

机构：

[1] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

[2] Karl Franzens Univ Graz, Inst Mol Biosci, Graz, Austria

[3] Heinrich Heine Univ, Dept Mol Med 2, Dusseldorf, Germany

[4] Med Univ Vienna, Dept Med 3, Div Endocrinol & Metab, Vienna, Austria

[5] German Canc Res Ctr, Div Chron Inflammat & Canc, Heidelberg, Germany

[6] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Div Gender & Mol Imaging, Preclin Imaging Lab, Vienna, Austria

[7] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland

[8] Seattle Childrens Res Inst, Ctr Global Infect Dis Res, Seattle, WA USA

来源：

NATURE IMMUNOLOGY | 2019年 / 20卷 / 06期

基金：

欧盟地平线“2020”; 奥地利科学基金会; 欧洲研究理事会; 美国国家卫生研究院;

关键词：

ADIPOSE-TISSUE; MOLECULAR-MECHANISMS; CLONAL EXPANSION; WASTING DISEASE; DEFICIENT MICE; IMMUNE; METABOLISM; GLUCOCORTICOIDS; EXPRESSION; INFLAMMATION;

D O I：

10.1038/s41590-019-0397-y

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Cachexia represents a leading cause of morbidity and mortality in various cancers, chronic inflammation and infections. Understanding of the mechanisms that drive cachexia has remained limited, especially for infection-associated cachexia (IAC). In the present paper we describe a model of reversible cachexia in mice with chronic viral infection and identify an essential role for CD8(+) T cells in IAC. Cytokines linked to cancer-associated cachexia did not contribute to IAC. Instead, virus-specific CD8(+) T cells caused morphologic and molecular changes in the adipose tissue, which led to depletion of lipid stores. These changes occurred at a time point that preceded the peak of the CD8(+) T cell response and required Tcell-intrinsic type I interferon signaling and antigen-specific priming. Our results link systemic antiviral immune responses to adipose-tissue remodeling and reveal an underappreciated role of CD8(+) T cells in IAC.

引用

页码：701 / +

页数：13

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