Open AccessRepression of bacterial lipoprotein production by F rancisella novicida facilitates evasion of innate immune recognition
Author(s) -
Jones Crystal L.,
Sampson Timothy R.,
Nakaya Helder I.,
Pulendran Bali,
Weiss David S.
Publication year - 2012
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/j.1462-5822.2012.01816.x
Subject(s) - tlr2 , biology , innate immune system , proinflammatory cytokine , microbiology and biotechnology , francisella tularensis , tularemia , francisella , immune system , tlr4 , immunology , inflammation , genetics , virulence , gene
Summary Innate recognition systems, including the T oll‐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, F rancisella novicida , modulates host defences to promote survival and replication in macrophages. TLR 2, which recognizes bacterial lipoproteins ( BLPs ), is critical for activating host defences and proinflammatory cytokine production in response to F rancisella infection. Here we show that the F . novicida protein FTN_0757 acts to repress BLP production, dampening TLR 2 activation. The Δ FTN_0757 mutant strain induced robust TLR 2‐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 TLR 2 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 TLR 2 activation, which is likely used by numerous other intracellular bacterial pathogens.