Title

The NLRP12 Inflammasome Recognizes Yersinia pestis

Student Author(s)

Gregory I. Vladimer; Dan Weng

GSBS 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

Date

7-27-2012

Document Type

Article

Medical Subject Headings

Immunity, Innate; Inflammasomes; Intracellular Signaling Peptides and Proteins; Interleukin-18; Interleukin-1beta; Yersinia pestis

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.

Comments

Citation: Immunity. 2012 Jul 27;37(1):96-107. DOI 10.1016/j.immuni.2012.07.006

Related Resources

Link to article in PubMed

Keywords

immunology, infectious disease, innate immunology

PubMed ID

22840842