Document Detail


Repression of bacterial lipoprotein production by Francisella novicida facilitates evasion of innate immune recognition.
MedLine Citation:
PMID:  22632124     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 ΔFTN_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 ΔFTN_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 ΔFTN_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.
Authors:
Crystal L Jones; Timothy R Sampson; Helder I Nakaya; Bali Pulendran; David S Weiss
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-06-12
Journal Detail:
Title:  Cellular microbiology     Volume:  14     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-14     Completed Date:  2013-01-28     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1531-43     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
Affiliation:
Department of Microbiology and Immunology, Microbiology and Molecular Genetics Program, Emory University, Atlanta, GA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Cytokines / secretion
Francisella tularensis / genetics,  immunology*,  pathogenicity*
Gene Deletion
Immune Evasion*
Lipoproteins / antagonists & inhibitors,  biosynthesis*,  genetics
Macrophages / immunology*,  microbiology*
Mice
Repressor Proteins / genetics,  metabolism*
Toll-Like Receptor 2 / metabolism
Virulence
Grant Support
ID/Acronym/Agency:
G20 RR030956/RR/NCRR NIH HHS; P30 CA68485/CA/NCI NIH HHS; P30 DK58404/DK/NIDDK NIH HHS; P30 EY08126/EY/NEI NIH HHS; P30NS055077/NS/NINDS NIH HHS; R56 AI087673/AI/NIAID NIH HHS; U54 AI057157/AI/NIAID NIH HHS; U54 AI057157/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Lipoproteins; 0/Repressor Proteins; 0/Tlr2 protein, mouse; 0/Toll-Like Receptor 2
Comments/Corrections

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