Thoracic adipose tissue contributes to severe virus infection of the lung

Franziska Hornung; Luise Schulz; Nilay Köse-Vogel; Antje Häder; Jana Grießhammer; Daniel Wittschieber; Angelina Autsch; Christina Ehrhardt; Gita Mall; Bettina Löffler; Stefanie Deinhardt-Emmer

doi:10.1038/s41366-023-01362-w

Thoracic adipose tissue contributes to severe virus infection of the lung

Int J Obes (Lond). 2023 Nov;47(11):1088-1099. doi: 10.1038/s41366-023-01362-w. Epub 2023 Aug 16.

Authors

Affiliations

¹ Institute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany. Franziska.hornung@med.uni-jena.de.
² Institute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany.
³ Institute of Forensic Medicine, Jena University Hospital, Am Klinikum 1, Jena, Germany.
⁴ Institute of Forensic Medicine, University Hospital Bonn, University of Bonn, Stiftsplatz 12, 53111, Bonn, Germany.
⁵ Section of Experimental Virology, Institute of Medical Microbiology, Center for Molecular Biomedicine (CMB), Jena University Hospital, Hans-Knoell-Straße 2, Jena, Germany.
⁶ Institute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany. Stefanie.deinhardt-emmer@med.uni-jena.de.
⁷ Leibniz Institute of Photonic Technology-Member of the Research Alliance "Leibniz Health Technologies", Albert-Einstein-Straße 9, Jena, Germany. Stefanie.deinhardt-emmer@med.uni-jena.de.

Abstract

Objective: Obesity is an independent risk factor for severe influenza virus and COVID-19 infections. There might be an interplay between adipose tissue and respiratory pathogens, although the mechanism is unknown. Proinflammatory factors secreted by the adipose tissue are often discussed to serve as indirect contributor to virus infection. However, the direct potential of adipose tissue to serve as a viral niche has not yet been investigated.

Methods: Two murine obesity models (DIO and ob/ob) were infected with influenza A virus (IAV) and monitored for 3 weeks. p.i. Lung and adipose tissue were harvested, and the viral load was analysed. Direct replication of IAV in vitro was investigated in human derived primary adipocytes and macrophages. The indirect impact of the secretory products of adipocytes during infection was analysed in a co-culture system with lung fibroblasts. Moreover, lung and adipose tissue was harvested from deceased patients infected with SARS-CoV-2 omicron variant. Additionally, replication of SARS-CoV-2 alpha, delta, and omicron variants was investigated in vitro in adipocytes and macrophages.

Results: Both murine obesity models presented high IAV titers compared to non-obese mice. Interestingly, adipose tissue adjacent to the lungs was a focal point for influenza virus replication in mice. We further detected IAV replication and antiviral response in human adipocytes. Co-cultivation of adipocytes and lung fibroblasts led to increased IL-8 concentration during infection. Though we observed SARS-CoV-2 in the thoracic adipose tissue of COVID-19 patients, no active replication was found in adipocytes in vitro. However, SARS-CoV-2 was detected in the macrophages and this finding was associated with increased inflammation.

Conclusions: Our study revealed that thoracic adipose tissue contributes to respiratory virus infection. Besides indirect induction of proinflammatory factors during infection, adipocytes and macrophages within the tissue can directly support viral replication.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue
Animals
COVID-19*
Humans
Influenza A virus* / physiology
Influenza, Human*
Lung
Mice
Obesity