• Cell reports · May 2019

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

    • Sulayman Benmerzoug, Badreddine Bounab, Stéphanie Rose, David Gosset, Franck Biet, Thierry Cochard, Aurore Xavier, Nathalie Rouxel, Louis Fauconnier, HorsnellWilliam G CWGCCNRS, UMR7355, Orléans 45071, France; Experimental and Molecular Immunology and Neurogenetics, University of Orléans, Orléans 45071, France; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town 7, Bernhard Ryffel, Dieudonnee Togbe, and QuesniauxValerie F JVFJCNRS, UMR7355, Orléans 45071, France; Experimental and Molecular Immunology and Neurogenetics, University of Orléans, Orléans 45071, France. Electronic address: quesniaux@cnrs-orleans.fr..
    • CNRS, UMR7355, Orléans 45071, France; Experimental and Molecular Immunology and Neurogenetics, University of Orléans, Orléans 45071, France.
    • Cell Rep. 2019 May 28; 27 (9): 2649-2664.e5.

    AbstractLung 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.Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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