NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens

Members of the intracellular nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family contribute to immune responses through activation of NF-κB, type I interferon and inflammasome signaling1. Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to col...

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Main Authors:	Anand, Paras K., Malireddi, R. K. Subbarao, Lukens, John R., Vogel, Peter, Bertin, John, Lamkanfi, Mohamed, Kanneganti, Thirumala-Devi
Format:	Online
Language:	English
Published:	2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422416/

id	pubmed-3422416
recordtype	oai_dc
spelling	pubmed-34224162013-02-16 NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens Anand, Paras K. Malireddi, R. K. Subbarao Lukens, John R. Vogel, Peter Bertin, John Lamkanfi, Mohamed Kanneganti, Thirumala-Devi Article Members of the intracellular nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family contribute to immune responses through activation of NF-κB, type I interferon and inflammasome signaling1. Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to colitis and colorectal tumorigenesis2-4, but the role of NLRP6 in microbial infections and the nature of the inflammatory signaling pathways regulated by NLRP6 remain unclear. Here, we show that Nlrp6-deficient mice were highly resistant to infection with the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. Infected Nlrp6-deficient mice had increased numbers of monocytes and neutrophils in circulation, and NLRP6 signaling in both hematopoietic and radio-resistant cells contributed to increased susceptibility. Nlrp6-deficiency enhanced activation of MAPK and canonical NF-κB upon TLR, but not cytosolic NOD1/2 ligation in vitro. Consequently, infected Nlrp6-deficient cells produced elevated levels of NF-κB- and MAPK-dependent cytokines and chemokines. Thus, our results reveal NLRP6 as a negative regulator of inflammatory signaling, and demonstrate a role for this NLR in impeding clearance of both Gram-positive and –negative bacterial pathogens. 2012-08-16 /pmc/articles/PMC3422416/ /pubmed/22763455 http://dx.doi.org/10.1038/nature11250 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Anand, Paras K. Malireddi, R. K. Subbarao Lukens, John R. Vogel, Peter Bertin, John Lamkanfi, Mohamed Kanneganti, Thirumala-Devi
spellingShingle	Anand, Paras K. Malireddi, R. K. Subbarao Lukens, John R. Vogel, Peter Bertin, John Lamkanfi, Mohamed Kanneganti, Thirumala-Devi NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens
author_facet	Anand, Paras K. Malireddi, R. K. Subbarao Lukens, John R. Vogel, Peter Bertin, John Lamkanfi, Mohamed Kanneganti, Thirumala-Devi
author_sort	Anand, Paras K.
title	NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens
title_short	NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens
title_full	NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens
title_fullStr	NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens
title_full_unstemmed	NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens
title_sort	nlrp6 negatively regulates innate immunity and host defense against bacterial pathogens
description	Members of the intracellular nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family contribute to immune responses through activation of NF-κB, type I interferon and inflammasome signaling1. Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to colitis and colorectal tumorigenesis2-4, but the role of NLRP6 in microbial infections and the nature of the inflammatory signaling pathways regulated by NLRP6 remain unclear. Here, we show that Nlrp6-deficient mice were highly resistant to infection with the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. Infected Nlrp6-deficient mice had increased numbers of monocytes and neutrophils in circulation, and NLRP6 signaling in both hematopoietic and radio-resistant cells contributed to increased susceptibility. Nlrp6-deficiency enhanced activation of MAPK and canonical NF-κB upon TLR, but not cytosolic NOD1/2 ligation in vitro. Consequently, infected Nlrp6-deficient cells produced elevated levels of NF-κB- and MAPK-dependent cytokines and chemokines. Thus, our results reveal NLRP6 as a negative regulator of inflammatory signaling, and demonstrate a role for this NLR in impeding clearance of both Gram-positive and –negative bacterial pathogens.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422416/
_version_	1611550617238503424

NLRP6 Negatively Regulates Innate Immunity and Host Defense Against Bacterial Pathogens

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