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A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2

An inflammatory form of phagocyte death evoked by the Gram-negative bacterium Vibrio (V.) vulnificus (WT) is one of hallmarks to promote their colonization, but the virulence factor and infectious mechanism involved in this process remain largely unknown. Here, we identified extracellular metallopro...

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Autores principales: Lee, Sei-Jung, Jung, Young Hyun, Kim, Jun Sung, Lee, Hyun Jik, Lee, Sang Hun, Lee, Kyu-Ho, Jang, Kyung Ku, Choi, Sang Ho, Han, Ho Jae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554522/
https://www.ncbi.nlm.nih.gov/pubmed/28848713
http://dx.doi.org/10.3389/fcimb.2017.00352
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author Lee, Sei-Jung
Jung, Young Hyun
Kim, Jun Sung
Lee, Hyun Jik
Lee, Sang Hun
Lee, Kyu-Ho
Jang, Kyung Ku
Choi, Sang Ho
Han, Ho Jae
author_facet Lee, Sei-Jung
Jung, Young Hyun
Kim, Jun Sung
Lee, Hyun Jik
Lee, Sang Hun
Lee, Kyu-Ho
Jang, Kyung Ku
Choi, Sang Ho
Han, Ho Jae
author_sort Lee, Sei-Jung
collection PubMed
description An inflammatory form of phagocyte death evoked by the Gram-negative bacterium Vibrio (V.) vulnificus (WT) is one of hallmarks to promote their colonization, but the virulence factor and infectious mechanism involved in this process remain largely unknown. Here, we identified extracellular metalloprotease VvpM as a new virulence factor and investigated the molecular mechanism of VvpM which acts during the regulation of the inflammatory form of macrophage death and bacterial colonization. Mutation of the vvpM gene appeared to play major role in the prevention of IL-1β production due to V. vulnificus infection in macrophage. However, the recombinant protein (r) VvpM caused IL-1β production coupled with necrotic cell death, which is highly susceptible to the knockdown of annexin A2 (ANXA2) located in both membrane lipid and non-lipid rafts. In lipid rafts, rVvpM recruited NOX enzymes coupled with ANXA2 to facilitate the production of ROS responsible for the epigenetic and transcriptional regulation of NF-κB in the IL-1β promoter. rVvpM acting on non-lipid rafts increased LC3 puncta formation and autophagic flux, which are required for the mRNA expression of Atg5 involved in the autophagosome formation process. The autophagy activation caused by rVvpM induced NLRP3 inflammasome-dependent caspase-1 activation in the promoting of IL-1β production. In mouse models of V. vulnificus infection, the VvpM mutant failed to elevate the level of pro-inflammatory responses closely related to IL-1β production and prevented bacterial colonization. These findings delineate VvpM efficiently regulates two pathogenic pathways that stimulate NF-κB-dependent IL-1β production and autophagy-mediated NLRP3 inflammasome via distinct spatial targeting by ANXA2.
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spelling pubmed-55545222017-08-28 A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2 Lee, Sei-Jung Jung, Young Hyun Kim, Jun Sung Lee, Hyun Jik Lee, Sang Hun Lee, Kyu-Ho Jang, Kyung Ku Choi, Sang Ho Han, Ho Jae Front Cell Infect Microbiol Microbiology An inflammatory form of phagocyte death evoked by the Gram-negative bacterium Vibrio (V.) vulnificus (WT) is one of hallmarks to promote their colonization, but the virulence factor and infectious mechanism involved in this process remain largely unknown. Here, we identified extracellular metalloprotease VvpM as a new virulence factor and investigated the molecular mechanism of VvpM which acts during the regulation of the inflammatory form of macrophage death and bacterial colonization. Mutation of the vvpM gene appeared to play major role in the prevention of IL-1β production due to V. vulnificus infection in macrophage. However, the recombinant protein (r) VvpM caused IL-1β production coupled with necrotic cell death, which is highly susceptible to the knockdown of annexin A2 (ANXA2) located in both membrane lipid and non-lipid rafts. In lipid rafts, rVvpM recruited NOX enzymes coupled with ANXA2 to facilitate the production of ROS responsible for the epigenetic and transcriptional regulation of NF-κB in the IL-1β promoter. rVvpM acting on non-lipid rafts increased LC3 puncta formation and autophagic flux, which are required for the mRNA expression of Atg5 involved in the autophagosome formation process. The autophagy activation caused by rVvpM induced NLRP3 inflammasome-dependent caspase-1 activation in the promoting of IL-1β production. In mouse models of V. vulnificus infection, the VvpM mutant failed to elevate the level of pro-inflammatory responses closely related to IL-1β production and prevented bacterial colonization. These findings delineate VvpM efficiently regulates two pathogenic pathways that stimulate NF-κB-dependent IL-1β production and autophagy-mediated NLRP3 inflammasome via distinct spatial targeting by ANXA2. Frontiers Media S.A. 2017-08-11 /pmc/articles/PMC5554522/ /pubmed/28848713 http://dx.doi.org/10.3389/fcimb.2017.00352 Text en Copyright © 2017 Lee, Jung, Kim, Lee, Lee, Lee, Jang, Choi and Han. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Lee, Sei-Jung
Jung, Young Hyun
Kim, Jun Sung
Lee, Hyun Jik
Lee, Sang Hun
Lee, Kyu-Ho
Jang, Kyung Ku
Choi, Sang Ho
Han, Ho Jae
A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2
title A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2
title_full A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2
title_fullStr A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2
title_full_unstemmed A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2
title_short A Vibrio vulnificus VvpM Induces IL-1β Production Coupled with Necrotic Macrophage Death via Distinct Spatial Targeting by ANXA2
title_sort vibrio vulnificus vvpm induces il-1β production coupled with necrotic macrophage death via distinct spatial targeting by anxa2
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554522/
https://www.ncbi.nlm.nih.gov/pubmed/28848713
http://dx.doi.org/10.3389/fcimb.2017.00352
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