Title
The NLRP12 Inflammasome Recognizes Yersinia pestis
Academic Program
Interdisciplinary Graduate Program
UMMS Affiliation
Department of Medicine, Division of Infectious Disease and Immunology; Department of Molecular Genetics and Microbiology; Department of Medicine, Division of Preventive and Behavioral Medicine
Publication Date
2012-07-27
Document Type
Article
Disciplines
Immunity | Immunology of Infectious Disease | Life Sciences | Medicine and Health Sciences | Pathogenic Microbiology
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.
Keywords
immunology, infectious disease, innate immunology
DOI of Published Version
10.1016/j.immuni.2012.07.006
Source
Immunity. 2012 Jul 27;37(1):96-107. DOI 10.1016/j.immuni.2012.07.006
Journal/Book/Conference Title
Immunity
Related Resources
PubMed ID
22840842
Repository Citation
Vladimer GI, Weng D, Paquette SW, Vanaja SK, Rathinam VA, Aune M, Conlon JE, Burbage JJ, Proulx MK, Liu Q, Reed GW, Mecsas JC, Iwakura Y, Bertin J, Goguen JD, Fitzgerald KA, Lien E. (2012). The NLRP12 Inflammasome Recognizes Yersinia pestis. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1016/j.immuni.2012.07.006. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1782