Open AccessSubversion of innate immune responses by Francisella involves the disruption of TRAF3 and TRAF6 signalling complexes
Author(s) -
Putzova Daniela,
Panda Swarupa,
Härtlova Anetta,
Stulík Jiří,
Gekara Nelson O.
Publication year - 2017
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12769
Subject(s) - francisella tularensis , biology , francisella , innate immune system , immune system , pattern recognition receptor , microbiology and biotechnology , tularemia , receptor , rig i , acquired immune system , virulence , immunology , gene , genetics
The success of pathogens depends on their ability to circumvent immune defences. Francisella tularensis is one of the most infectious bacteria known. The remarkable virulence of Francisella is believed to be due to its capacity to evade or subvert the immune system, but how remains obscure. Here, we show that Francisella triggers but concomitantly inhibits the Toll‐like receptor, RIG‐I‐like receptor, and cytoplasmic DNA pathways. Francisella subverts these pathways at least in part by inhibiting K63‐linked polyubiquitination and assembly of TRAF6 and TRAF3 complexes that control the transcriptional responses of pattern recognition receptors. We show that this mode of inhibition requires a functional type VI secretion system and/or the presence of live bacteria in the cytoplasm. The ability of Francisella to enter the cytosol while simultaneously inhibiting multiple pattern recognition receptor pathways may account for the notable capacity of this bacterium to invade and proliferate in the host without evoking a self‐limiting innate immune response.