Subversion of innate immune responses by Francisella involves the disruption of TRAF3 and TRAF6 signaling complexes

Summary
The success of pathogens depends on their ability to circumvent immune defenses. 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 (TLR), RIG‐I‐like receptor (RLR) and Cytoplasmic DNA (CDR) 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 PRRs. 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 PRR 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.

Source: Cellular Microbiology - July 26, 2017 Category: Microbiology Authors: Daniela Putzova, Swarupa Panda, Anetta H ärtlova, Jiří Stulík, Nelson O. Gekara Tags: RESEARCH ARTICLE Source Type: research