The NLRP12 Inflammasome Recognizes Yersinia pestis

Vladimer, Gregory I.; Weng, Dan; Paquette, Sara W. Montminy; Vanaja, Sivapriya Kailasan; Rathinam, Vijay; Aune, Marie; Conlon, Joseph E.; Burbage, Joseph J.; Proulx, Megan K.; Liu, Qin; Reed, George W.; Mecsas, Joan; Iwakura, Yoichiro; Bertin, John; Goguen, Jon D.; Fitzgerald, Katherine A.; Lien, Egil

doi:10.1016/j.immuni.2012.07.006

Cited by 328 publications

(254 citation statements)

References 66 publications

(94 reference statements)

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“…Indeed, one study showed that NLRP12 drives inflammasome-dependent responses following Yersinia infection (18). Another study found that TDP from M. tuberculosis and LPS from K. pneumoniae induced increased levels of TNF-α and IL-6 in Nlrp12 −/− bone marrow-derived DCs more significantly than in WT cells, suggesting that NLRP12 plays a role in suppressing NF-κB signaling in response to these bacterial components (13).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Vladimer et al (18) showed that NLRP12 activates caspase-1 and generates IL-18 production by assembling an inflammasome in response to infection by Y. pestis. To investigate whether NLRP12 triggers inflammasome activation in response to Salmonella infection, we infected WT and Nlrp12 −/− BMDMs with S. typhimurium and examined caspase-1 proteolysis and IL-1β production.…”

Section: Nlrp12-mediated Inhibition Of Proinflammatory and No Productionmentioning

confidence: 99%

“…Vladimer et al (18) reported that Nlrp12 −/− mice are hypersusceptible to Yersinia pestis infection, whereby NLRP12 is required to drive caspase-1 activation and IL-1β and IL-18 release. Another study found that WT and Nlrp12 −/− mice exhibit similar host innate responses in lung infections induced by Mycobacterium tuberculosis or Klebsiella pneumoniae (13).…”

mentioning

confidence: 99%

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Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection

Zaki¹,

Man²,

Vogel

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

129

128

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The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 12 (NLRP12) plays a protective role in intestinal inflammation and carcinogenesis, but the physiological function of this NLR during microbial infection is largely unexplored. Salmonella enterica serovar Typhimurium (S. typhimurium) is a leading cause of food poisoning worldwide. Here, we show that NLRP12-deficient mice were highly resistant to S. typhimurium infection. Salmonella-infected macrophages induced NLRP12-dependent inhibition of NF-κB and ERK activation by suppressing phosphorylation of IκBα and ERK. NLRP12-mediated downregulation of proinflammatory and antimicrobial molecules prevented efficient clearance of bacterial burden, highlighting a role for NLRP12 as a negative regulator of innate immune signaling during salmonellosis. These results underscore a signaling pathway defined by NLRP12-mediated dampening of host immune defenses that could be exploited by S. typhimurium to persist and survive in the host.

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Section: Discussionmentioning

confidence: 99%

Section: Nlrp12-mediated Inhibition Of Proinflammatory and No Productionmentioning

confidence: 99%

mentioning

confidence: 99%

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Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection

Zaki¹,

Man²,

Vogel

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

129

128

View full text Add to dashboard Cite

show abstract

“…It functions asYersinia pestis recognition and inflammasome formation for IL-1b and IL-18 maturation for host defense. Meanwhile, it also suppresses colon inflammation and tumorigenesis through negatively regulating the canonical or non-canonical NF-κB signaling (Zaki et al, 2011;Allen et al, 2012;Vladimer et al, 2012). NLRP7 forms infl ammasome during recognition of microbial lipopeptides in human macrophages (Khare et al, 2012).…”

Section: Expression Of Nlrc5mentioning

confidence: 99%

Expression regulation and function of NLRC5

Yao

Qian

2013

Protein Cell

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The NOD like receptors (NLRs), a class of intracellular receptors that respond to pathogen attack or cellular stress, have gained increasing attention. NLRC5, the largest member of the NLR protein family, has recently been identified as a critical regulator of immune responses. While NLRC5 is constitutively and widely expressed, it can be dramatically induced by interferons during pathogen infections. Both in vitro and in vivo studies have demonstrated that NLRC5 is a specifi c and master regulator of major mistocompatibility complex (MHC) class I genes as well as related genes involved in MHC class I antigen presentation. The expression of MHC class I genes is regulated by NLRC5 in coordination with the RFX components through an enhanceosome-dependent manner. And the involvement of NLRC5 in MHC class I mediated CD8 + T cell activation, proliferation and cytotoxicity is proved to be critical for host defense against intracellular bacterial infections. Nevertheless, the role of NLRC5 in innate immunity remains to be further explored. Here, we review the research advances on the structure, expression regulation and function of NLRC5.

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“…New members of the NLR family (NLRP6 and 12) also induce inflamma some activation in an ASC-caspase 1 dependent fashion 38,39 .…”

Section: Nod-like Receptorsmentioning

confidence: 99%