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- Title
Repression of bacterial lipoprotein production by Francisella novicida facilitates evasion of innate immune recognition.
- Authors
Jones, Crystal L.; Sampson, Timothy R.; Nakaya, Helder I.; Pulendran, Bali; Weiss, David S.
- Abstract
Innate recognition systems, including the Toll-like receptors ( TLRs), play a critical role in activating host defences and proinflammatory pathways in response to infection. Pathogens have developed strategies to subvert TLRs in order to survive and replicate within the host. The model intracellular pathogen, Francisella novicida, modulates host defences to promote survival and replication in macrophages. TLR2, which recognizes bacterial lipoproteins ( BLPs), is critical for activating host defences and proinflammatory cytokine production in response to Francisella infection. Here we show that the F. novicida protein FTN_0757 acts to repress BLP production, dampening TLR2 activation. The Δ FTN_0757 mutant strain induced robust TLR2-dependent cytokine production in macrophages compared with wild-type bacteria, and produced increased amounts of BLPs. The deletion of one BLP ( FTN_1103) from Δ FTN_0757 decreased the total BLP concentration to near wild-type level sand correlated with a decrease in the inductionof TLR2 signalling. The overproduction of BLPs also contributed to the in vivo attenuation of the Δ FTN_0757 mutant, which was significantly rescued when FTN_1103 was deleted. Taken together, these data reveal a novel mechanism of immune evasion by the downregulation of BLP expression to subvert TLR2 activation, which is likely used by numerous other intracellular bacterial pathogens.
- Subjects
LIPOPROTEINS; FRANCISELLA novicida; BACTERIA; NATURAL immunity; IMMUNE recognition; TOLL-like receptors; INFLAMMATION; PATHOGENIC microorganisms
- Publication
Cellular Microbiology, 2012, Vol 14, Issue 10, p1531
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/j.1462-5822.2012.01816.x