The NLRP12 Inflammasome Recognizes Yersinia pestis
Interdisciplinary Graduate Program
Department of Medicine, Division of Infectious Disease and Immunology; Department of Molecular Genetics and Microbiology; Department of Medicine, Division of Preventive and Behavioral Medicine
Medical Subject Headings
Immunity, Innate; Inflammasomes; Intracellular Signaling Peptides and Proteins; Interleukin-18; Interleukin-1beta; Yersinia pestis
Immunity | Immunology of Infectious Disease | Life Sciences | Medicine and Health Sciences | Pathogenic Microbiology
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.
immunology, infectious disease, innate immunology
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.; and Lien, Egil, "The NLRP12 Inflammasome Recognizes Yersinia pestis" (2012). GSBS Student Publications. Paper 1782.