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Review
. 2020 Dec:76:100887.
doi: 10.1016/j.mam.2020.100887. Epub 2020 Aug 22.

NLRP12 in innate immunity and inflammation

Shraddha Tuladhar  1 , Thirumala-Devi Kanneganti  2
Affiliations
Review

NLRP12 in innate immunity and inflammation

Shraddha Tuladhar et al. Mol Aspects Med. 2020 Dec.

Abstract

Nucleotide-binding leucine-rich repeat-containing proteins, or NOD-like receptors (NLRs), are intracellular innate immune sensors that can regulate several signaling pathways, including MyD88- and TRIF-dependent pathways. In addition to these regulatory roles, some NLRs can assemble into multimeric protein complexes known as inflammasomes. NLRP12 is a member of the NLR family that contains an N-terminal pyrin domain, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat. It has been shown to play a role in forming an inflammasome in response to specific infections, and it can also function as a regulator of inflammatory signaling. During Yersinia pestis or Plasmodium chabaudi infection, NLRP12 induces the release of the inflammasome-dependent cytokines IL-1β and IL-18. These NLRP12-dependent cytokines confer protection against severe infections caused by these pathogens. Conversely, during infection with Salmonella enterica serovar Typhimurium, vesicular stomatitis virus, Klebsiella pneumoniae, or Mycobacterium tuberculosis, and in colonic tumorigenesis, NLRP12 acts as a negative regulator of the NFκB and MAPK signaling pathways. NLRP12 also negatively regulates canonical and non-canonical signaling in T cells and causes exacerbated autoimmune diseases. Furthermore, NLRP12 acts as a central component in maintaining intestinal inflammation and gut homeostasis. Therefore, the ability of NLRP12 to function as an inflammasome or as a negative regulator is context-dependent. In this review, we provide an overview of the NLR family members and summarize recent insights into the roles of NLRP12 as an inflammasome and as a negative regulator.

Keywords: ASC; Cancer; Caspase-1; Cell death; Gasdermin; IL-18; IL-1β; Infection; Inflammasome; Inflammation; NLRP12; Negative regulator; Pyrin domain; Pyroptosis.

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Conflict of interest statement

Conflicts of Interest

The authors have no conflicts of interest to disclose.

Figures

Figure 1:
Figure 1:
Schematic representation of NLR family members, including members of the NLRC and NLRP groups. The arrow indicates that NLRP2 to NLRP9 and NLRP11 to NLRP14 share the same domains. AD, activation domain; BIR, baculovirus inhibitor of apoptosis protein repeat; CARD, caspase recruitment domain; CIITA, class II major histocompatibility complex transactivator; FIIND, function to find domain; LRR, leucine-rich repeats; NACHT domain, NAIP, CIITA, HET-E, and TP1-containing domain; NBD, nucleotide-binding domain; PYD, pyrin domain.
Figure 2:
Figure 2:
NLRP12 acts in innate immune signaling in a pathogen-specific manner. (A) NLRP12 negatively regulates inflammatory signaling by suppressing canonical and non-canonical NFκB signaling and the MAPK/ERK signaling pathway in bone marrow-derived macrophages (BMDMs)002E (B) NLRP12 associates with TRIM25 to reduce polyubiquitination and inhibit the RIG-I-mediated IFN response during VSV infection. (C) The NLRP12 inflammasome can drive caspase-1 activation and IL-1β and IL-18 release in BMDMs during infection with Yersinia pestis and Plasmodium chabaudi.
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