Stiftung Tierärztliche Hochschule Hannover (TiHo)

Blocking IL-10 receptor signaling ameliorates Mycobacterium tuberculosis infection during influenza-induced exacerbation

Affiliation
Junior Research Group Coinfection, Priority Research Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Ring, Sarah;
Affiliation
Junior Research Group Coinfection, Priority Research Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Eggers, Lars;
Affiliation
Core Facility Fluorescence Cytometry, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Behrends, Jochen;
Affiliation
Bioanalytical Chemistry, Priority Research Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Wutkowski, Adam;
ORCID
0000-0002-1379-9451
Affiliation
Bioanalytical Chemistry, Priority Research Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Schwudke, Dominik;
Affiliation
Institute of Medical Microbiology and Hospital Hygiene, Otto-von-Guericke-University Magdeburg, and Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Kröger, Andrea;
Affiliation
Department of Obstetrics and Fetal Medicine, Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hierweger, Alexandra Maximiliane;
Affiliation
Infection Immunology, Priority Research Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Hölscher, Christoph;
ORCID
0000-0003-0542-8033
Affiliation
Research Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Gabriel, Gülsah;
Affiliation
Junior Research Group Coinfection, Priority Research Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Schneider, Bianca E.

Epidemiological findings indicate that coinfection with influenza viruses is associated with an increased risk of death in patients suffering from tuberculosis but the underlying pathomechanisms are not well understood. In this study, we demonstrate that influenza A virus (IAV) coinfection rapidly impairs control of Mycobacterium tuberculosis (Mtb) in C57BL/6 mice. IAV coinfection was associated with significantly increased bacterial loads, reduced survival and a substantial modulation of innate and adaptive immune defenses including an impaired onset and development of Mtb-specific CD4+ T cell responses and the accumulation of macrophages with increased arginase-1 production in the lungs. Our findings strongly indicate that IAV coinfection compromises the host's ability to control Mtb infection via the production of IL-10 which was rapidly induced upon viral infection. The blockade of IL-10 receptor signaling reduced the bacterial load in coinfected mice to a level comparable with that in Mtb-only-infected animals. Taken together, our data suggest that IL-10 signaling constitutes a major pathway that enhances susceptibility to Mtb during concurrent IAV infection.

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