title: The NLRP12 inflammasome recognizes Yersinia pestis.
abstract: 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.
authors: Division of Infectious Diseases and Immunology, UMass Medical School, Worcester, MA 01605, USA.
authors: Gregory I
authors: GI
authors: Vladimer
authors: Dan
authors: D
authors: Weng
authors: Sara W Montminy
authors: SW
authors: Paquette
authors: Sivapriya Kailasan
authors: SK
authors: Vanaja
authors: Vijay A K
authors: VA
authors: Rathinam
authors: Marie Hjelmseth
authors: MH
authors: Aune
authors: Joseph E
authors: JE
authors: Conlon
authors: Joseph J
authors: JJ
authors: Burbage
authors: Megan K
authors: MK
authors: Proulx
authors: Qin
authors: Q
authors: Liu
authors: George
authors: G
authors: Reed
authors: Joan C
authors: JC
authors: Mecsas
authors: Yoichiro
authors: Y
authors: Iwakura
authors: John
authors: J
authors: Bertin
authors: Jon D
authors: JD
authors: Goguen
authors: Katherine A
authors: KA
authors: Fitzgerald
authors: Egil
authors: E
authors: Lien
mesh_terms: D000818:Animals; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010930:Plague / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality; D015398:Signal Transduction; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D047908:Intracellular Signaling Peptides and Proteins; C553199:NLRP12 protein, mouse; D007371:Interferon-gamma