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Subversion of innate immune responses by Francisella involves the disruption of TRAF3 and TRAF6 signalling complexes
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå university. (Nelson O Gekara)
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2017 (English)In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 19, no 11, article id e12769Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Hoboken: Wiley-Blackwell, 2017. Vol. 19, no 11, article id e12769
Keywords [en]
inflammatory responses, listeria monocytogenes, murine macrophages, tularensis lvs, cytosolic dna, in vitro, system, infection, activation, trif
National Category
Cell and Molecular Biology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:umu:diva-139636DOI: 10.1111/cmi.12769ISI: 000412834200008OAI: oai:DiVA.org:umu-139636DiVA, id: diva2:1142413
Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2018-06-09Bibliographically approved

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Panda, Swarupa

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Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)Umeå Centre for Microbial Research (UCMR)
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