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XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection

The inhibitor of apoptosis protein (IAP) family has been implicated in immune regulation, but the mechanisms by which IAP proteins contribute to immunity are incompletely understood. We show here that X-linked IAP (XIAP) is required for innate immune control of Listeria monocytogenes infection. Mice...

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Detalles Bibliográficos
Autores principales: Bauler, Laura D., Duckett, Colin S., O'Riordan, Mary X. D.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516935/
https://www.ncbi.nlm.nih.gov/pubmed/18769721
http://dx.doi.org/10.1371/journal.ppat.1000142
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author Bauler, Laura D.
Duckett, Colin S.
O'Riordan, Mary X. D.
author_facet Bauler, Laura D.
Duckett, Colin S.
O'Riordan, Mary X. D.
author_sort Bauler, Laura D.
collection PubMed
description The inhibitor of apoptosis protein (IAP) family has been implicated in immune regulation, but the mechanisms by which IAP proteins contribute to immunity are incompletely understood. We show here that X-linked IAP (XIAP) is required for innate immune control of Listeria monocytogenes infection. Mice deficient in XIAP had a higher bacterial burden 48 h after infection than wild-type littermates, and exhibited substantially decreased survival. XIAP enhanced NF-κB activation upon L. monocytogenes infection of activated macrophages, and prolonged phosphorylation of Jun N-terminal kinase (JNK) specifically in response to cytosolic bacteria. Additionally, XIAP promoted maximal production of pro-inflammatory cytokines upon bacterial infection in vitro or in vivo, or in response to combined treatment with NOD2 and TLR2 ligands. Together, our data suggest that XIAP regulates innate immune responses to L. monocytogenes infection by potentiating synergy between Toll-like receptors (TLRs) and Nod-like receptors (NLRs) through activation of JNK- and NF-κB–dependent signaling.
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spelling pubmed-25169352008-08-29 XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection Bauler, Laura D. Duckett, Colin S. O'Riordan, Mary X. D. PLoS Pathog Research Article The inhibitor of apoptosis protein (IAP) family has been implicated in immune regulation, but the mechanisms by which IAP proteins contribute to immunity are incompletely understood. We show here that X-linked IAP (XIAP) is required for innate immune control of Listeria monocytogenes infection. Mice deficient in XIAP had a higher bacterial burden 48 h after infection than wild-type littermates, and exhibited substantially decreased survival. XIAP enhanced NF-κB activation upon L. monocytogenes infection of activated macrophages, and prolonged phosphorylation of Jun N-terminal kinase (JNK) specifically in response to cytosolic bacteria. Additionally, XIAP promoted maximal production of pro-inflammatory cytokines upon bacterial infection in vitro or in vivo, or in response to combined treatment with NOD2 and TLR2 ligands. Together, our data suggest that XIAP regulates innate immune responses to L. monocytogenes infection by potentiating synergy between Toll-like receptors (TLRs) and Nod-like receptors (NLRs) through activation of JNK- and NF-κB–dependent signaling. Public Library of Science 2008-08-29 /pmc/articles/PMC2516935/ /pubmed/18769721 http://dx.doi.org/10.1371/journal.ppat.1000142 Text en Bauler et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bauler, Laura D.
Duckett, Colin S.
O'Riordan, Mary X. D.
XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection
title XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection
title_full XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection
title_fullStr XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection
title_full_unstemmed XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection
title_short XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection
title_sort xiap regulates cytosol-specific innate immunity to listeria infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516935/
https://www.ncbi.nlm.nih.gov/pubmed/18769721
http://dx.doi.org/10.1371/journal.ppat.1000142
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