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Blocking IL-10 receptor signaling ameliorates Mycobacterium tuberculosis infection during influenza-induced exacerbation
Sarah Ring, … , Gülsah Gabriel, Bianca E. Schneider
Sarah Ring, … , Gülsah Gabriel, Bianca E. Schneider
Published April 18, 2019
Citation Information: JCI Insight. 2019;4(10):e126533. https://doi.org/10.1172/jci.insight.126533.
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Research Article Immunology Infectious disease

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

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Abstract

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 to 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.

Authors

Sarah Ring, Lars Eggers, Jochen Behrends, Adam Wutkowski, Dominik Schwudke, Andrea Kröger, Alexandra Maximiliane Hierweger, Christoph Hölscher, Gülsah Gabriel, Bianca E. Schneider

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Figure 1

IAV coinfection impairs control of Mtb.

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IAV coinfection impairs control of Mtb.
(A) Timeline of experimental set...
(A) Timeline of experimental setup. (B and C) C57BL/6 mice were infected via aerosol with a low dose of Mtb H37Rv and 12 days later coinfected i.n. with 1 × 104 PFU IAV (A/HH/05/09 H1N1). At indicated time points, bacterial burden in lung (B) and spleen (C) were determined (n = 6 [day 1, day 12 Mtb], n = 7–9 per group, data pooled from 2 independent experiments). (D and E) C57BL/6 mice received high-dose Mtb H37Rv aerosol infection and were coinfected i.n. with 1 × 104 PFU IAV (A/HH/05/09 H1N1) 12 days later. (D) At indicated time points, pulmonary bacterial burden (n = 3; day 1, day 12 Mtb; n = 4–5 per group, data from 1 experiment) was determined. (E) Mice were monitored for survival (n = 8–9 per group, data from 1 experiment) until day 250 after Mtb infection. (B–D) Each data point represents 1 mouse. *P ≤ 0.05; **P ≤ 0.01, ***P ≤ 0.001 determined by (B and C) unpaired t test and (E) log-rank (Mantel-Cox) test.
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