AuthorsVladimer, Gregory I.
Paquette, Sara W. Montminy
Vanaja, Sivapriya Kailasan
Rathinam, Vijay A.K.
Aune, Marie Hjelmseth
Conlon, Joseph E.
Burbage, Joseph J.
Proulx, Megan K.
Reed, George W.
Mecsas, Joan C.
Goguen, Jon D.
Fitzgerald, Katherine A.
Student AuthorsGregory I. Vladimer; Dan Weng
UMass Chan AffiliationsDepartment of Medicine, Division of Preventive and Behavioral Medicine
Department of Molecular Genetics and Microbiology
Department of Medicine, Division of Infectious Disease and Immunology
Document TypeJournal Article
KeywordsImmunity, Innate; Inflammasomes; Intracellular Signaling Peptides and Proteins; Interleukin-18; Interleukin-1beta; Yersinia pestis
Immunology of Infectious Disease
Medicine and Health Sciences
MetadataShow full item record
AbstractYersinia 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.
Immunity. 2012 Jul 27;37(1):96-107. DOI 10.1016/j.immuni.2012.07.006
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33248
Related ResourcesLink to article in PubMed