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Authors
Vladimer, Gregory I.Weng, Dan
Paquette, Sara W. Montminy
Vanaja, Sivapriya Kailasan
Rathinam, Vijay A.K.
Aune, Marie Hjelmseth
Conlon, Joseph E.
Burbage, Joseph J.
Proulx, Megan K.
Liu, Qin
Reed, George W.
Mecsas, Joan C.
Iwakura, Yoichiro
Bertin, John
Goguen, Jon D.
Fitzgerald, Katherine A.
Lien, Egil
Student Authors
Gregory I. Vladimer; Dan WengUMass Chan Affiliations
Department of Medicine, Division of Preventive and Behavioral MedicineDepartment of Molecular Genetics and Microbiology
Department of Medicine, Division of Infectious Disease and Immunology
Document Type
Journal ArticlePublication Date
2012-07-27Keywords
Immunity, Innate; Inflammasomes; Intracellular Signaling Peptides and Proteins; Interleukin-18; Interleukin-1beta; Yersinia pestisimmunology
infectious disease
innate immunology
Immunity
Immunology of Infectious Disease
Life Sciences
Medicine and Health Sciences
Pathogenic Microbiology
Metadata
Show full item recordAbstract
Yersinia pestis, the causative agent of plague, is able to suppress production of inflammatory cytokines IL-18 and IL-1β, which are generated through caspase-1-activating nucleotide-binding domain and leucine-rich repeat (NLR)-containing inflammasomes. Here, we sought to elucidate the role of NLRs and IL-18 during plague. Lack of IL-18 signaling led to increased susceptibility to Y. pestis, producing tetra-acylated lipid A, and an attenuated strain producing a Y. pseudotuberculosis-like hexa-acylated lipid A. We found that the NLRP12 inflammasome was an important regulator controlling IL-18 and IL-1β production after Y. pestis infection, and NLRP12-deficient mice were more susceptible to bacterial challenge. NLRP12 also directed interferon-γ production via induction of IL-18, but had minimal effect on signaling to the transcription factor NF-κB. These studies reveal a role for NLRP12 in host resistance against pathogens. Minimizing NLRP12 inflammasome activation may have been a central factor in evolution of the high virulence of Y. pestis.Source
Immunity. 2012 Jul 27;37(1):96-107. DOI 10.1016/j.immuni.2012.07.006
DOI
10.1016/j.immuni.2012.07.006Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33248PubMed ID
22840842Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2012.07.006