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Article Dans Une Revue Cell Reports Année : 2019

Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity

David Gosset
Franck Biet
Nathalie Rouxel
  • Fonction : Auteur
Louis Fauconnier
  • Fonction : Auteur

Résumé

Lung inflammation induced by silica impairs host control of tuberculosis, yet the underlying mechanism remains unclear. Here, we show that silica-driven exacerbation of M. tuberculosis infection associates with raised type 2 immunity. Silica increases pulmonary Th2 cell and M2 macrophage responses, while reducing type 1 immunity after M. tuberculosis infection. Silica induces lung damage that prompts extracellular self-DNA release and activates STING. This STING priming potentiates M. tuberculosis DNA sensing by and activation of cGAS/STING, which triggers enhanced type I interferon (IFNI) response and type 2 immunity. cGAS-, STING-, and IFNAR-deficient mice are resistant to silica-induced exacerbation of M. tuberculosis infection. Thus, silica-induced self-DNA primes the host response to M. tuberculosis-derived nucleic acids, which increases type 2 immunity while reducing type 1 immunity, crucial for controlling M. tuberculosis infection. These data show how cGAS/STING pathway activation, at the crossroads of sterile inflammation and infection, may affect the host response to pathogens such as M. tuberculosis.
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Dates et versions

hal-02147129 , version 1 (26-05-2020)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Sulayman Benmerzoug, Badreddine Bounab, Stéphanie Rose, David Gosset, Franck Biet, et al.. Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity. Cell Reports, 2019, 27 (9), pp.2649-2664.e5. ⟨10.1016/j.celrep.2019.04.110⟩. ⟨hal-02147129⟩
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