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Cutting Edge: Mycobacterium tuberculosis but Not Nonvirulent Mycobacteria Inhibits IFN-β and AIM2 Inflammasome–Dependent IL-1β Production via Its ESX-1 Secretion System

Year: 2013
Type: article
Abstract: Mycobacterium tuberculosis extracellular DNA gains access to the host cell cytosol via the ESX-1 secretion system. It is puzzling that this extracellular DNA of M. tuberculosis does not induce activation of the AIM2 inflammasome because AIM2 recognizes cytosolic DNA. In this study, we show that nonvirulent mycobacteria such as Mycobacterium smegmatis induce AIM2 inflammasome activation, which is dependent on their strong induction of IFN-β production. In contrast, M. tuberculosis, but not an ESX-1-deficient mutant, inhibits the AIM2 inflammasome activation induced by either M. smegmatis or transfected dsDNA. The inhibition does not involve changes in host cell AIM2 mRNA or protein levels but led to decreased activation of caspase-1. We furthermore demonstrate that M. tuberculosis inhibits IFN-β production and signaling, which was partially responsible for the inhibition of AIM2 activation. In conclusion, we report a novel immune evasion mechanism of M. tuberculosis that involves the ESX-1-dependent, direct or indirect, suppression of the host cell AIM2 inflammasome activation during infection.
DOI: 10.4049/jimmunol.1301331
Authors: Swati Shah, Amro Bohsali, Sarah E Ahlbrand, Lalitha Srinivasan, Vijay A K Rathinam, Stefanie N Vogel, Katherine A Fitzgerald, Fayyaz S Sutterwala, Volker Briken
Institutions: University of Maryland, College Park, University of Massachusetts Chan Medical School, University of Maryland, Baltimore, University of Iowa, Veterans Health Administration, Iowa City VA Medical Center
Language: English
Field: Medicine
Open Access status: bronze
Awards: Nlrp3 inflammasome signaling in immune responses to Candida albicans, G1334660776, G219369639, G2214131976, G2270832713, G2478318263, G255176686, G2837653780, Mechanism of host cell apoptosis inhibition by Mycobacterium tuberculosis, G3013704077, Mechanism of host cell apoptosis inhibition by Mycobacterium tuberculosis, G3683497028, G500513763, G5769833972, DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATION, G604311963, G6751140813, G6931532595, G694731757, G9000025611, G9000141122, G9000217054, G9000339175, Environmental Health Sciences Research Center
OpenAlex ID: W2122611554
FWCI: 8.973
Cites: 23
Cited by: 124
Related to: 10