The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses

Host engulfment protein ELMO1 generates intestinal inflammation following internalization of enteric bacteria. In Shigella, bacterial effector IpgB1 interacts with ELMO1 and promotes bacterial invasion. IpgB1 belongs to the WxxxE effector family, a motif found in several effectors of enteric pathoge...

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Autores principales:	Ibrahim M Sayed, Stella-Rita Ibeawuchi, Dominique Lie, Mahitha Shree Anandachar, Rama Pranadinata, Manuela Raffatellu, Soumita Das
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	elmo1 bacterial effectors wxxxe motif commensals innate immune response Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/d7b9dca0753d4394bab8eb20083824c4
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spelling	oai:doaj.org-article:d7b9dca0753d4394bab8eb20083824c42021-11-26T11:19:48ZThe interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses1949-09761949-098410.1080/19490976.2021.1991776https://doaj.org/article/d7b9dca0753d4394bab8eb20083824c42021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1991776https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Host engulfment protein ELMO1 generates intestinal inflammation following internalization of enteric bacteria. In Shigella, bacterial effector IpgB1 interacts with ELMO1 and promotes bacterial invasion. IpgB1 belongs to the WxxxE effector family, a motif found in several effectors of enteric pathogens. Here, we have studied the role of WxxxE effectors, with emphasis on Salmonella SifA and whether it interacts with ELMO1 to regulate inflammation. In-silico-analysis of WxxxE effectors was performed using BLAST search and Clustal W program. The interaction of ELMO1 with SifA was assessed by GST pulldown assay and co-immunoprecipitation. ELMO1 knockout mice, and ELMO1-depleted murine macrophage J774 cell lines were challenged with WT and SifA mutant Salmonella. Bacterial effectors containing the WxxxE motif were transfected in WT and ELMO1-depleted J774 cells to assess the inflammatory cytokines. ELMO1 generates differential pro-inflammatory cytokines between pathogenic and nonpathogenic bacteria. WxxxE motif is present in pathogens and in the TIR domain of host proteins. The C-terminal part of ELMO1 interacts with SifA where WxxxE motif is important for interaction. ELMO1–SifA interaction affects bacterial colonization, dissemination, and inflammatory cytokines in vivo. Moreover, ELMO1–SifA interaction increases TNF-α and IL-6 production from the macrophage cell line and is associated with enhanced Rac1 activity. ELMO1 also interacts with WxxxE effectors IpgB1, IpgB2, and Map and induces inflammation after challenge with microbes or microbial ligands. ELMO1 generates a differential response through interaction with the WxxxE motif, which is absent in commensals. ELMO1-WxxxE interaction plays a role in bacterial pathogenesis and induction of inflammatory response.Ibrahim M SayedStella-Rita IbeawuchiDominique LieMahitha Shree AnandacharRama PranadinataManuela RaffatelluSoumita DasTaylor & Francis Grouparticleelmo1bacterial effectorswxxxe motifcommensalsinnate immune responseDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	elmo1 bacterial effectors wxxxe motif commensals innate immune response Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	elmo1 bacterial effectors wxxxe motif commensals innate immune response Diseases of the digestive system. Gastroenterology RC799-869 Ibrahim M Sayed Stella-Rita Ibeawuchi Dominique Lie Mahitha Shree Anandachar Rama Pranadinata Manuela Raffatellu Soumita Das The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
description	Host engulfment protein ELMO1 generates intestinal inflammation following internalization of enteric bacteria. In Shigella, bacterial effector IpgB1 interacts with ELMO1 and promotes bacterial invasion. IpgB1 belongs to the WxxxE effector family, a motif found in several effectors of enteric pathogens. Here, we have studied the role of WxxxE effectors, with emphasis on Salmonella SifA and whether it interacts with ELMO1 to regulate inflammation. In-silico-analysis of WxxxE effectors was performed using BLAST search and Clustal W program. The interaction of ELMO1 with SifA was assessed by GST pulldown assay and co-immunoprecipitation. ELMO1 knockout mice, and ELMO1-depleted murine macrophage J774 cell lines were challenged with WT and SifA mutant Salmonella. Bacterial effectors containing the WxxxE motif were transfected in WT and ELMO1-depleted J774 cells to assess the inflammatory cytokines. ELMO1 generates differential pro-inflammatory cytokines between pathogenic and nonpathogenic bacteria. WxxxE motif is present in pathogens and in the TIR domain of host proteins. The C-terminal part of ELMO1 interacts with SifA where WxxxE motif is important for interaction. ELMO1–SifA interaction affects bacterial colonization, dissemination, and inflammatory cytokines in vivo. Moreover, ELMO1–SifA interaction increases TNF-α and IL-6 production from the macrophage cell line and is associated with enhanced Rac1 activity. ELMO1 also interacts with WxxxE effectors IpgB1, IpgB2, and Map and induces inflammation after challenge with microbes or microbial ligands. ELMO1 generates a differential response through interaction with the WxxxE motif, which is absent in commensals. ELMO1-WxxxE interaction plays a role in bacterial pathogenesis and induction of inflammatory response.
format	article
author	Ibrahim M Sayed Stella-Rita Ibeawuchi Dominique Lie Mahitha Shree Anandachar Rama Pranadinata Manuela Raffatellu Soumita Das
author_facet	Ibrahim M Sayed Stella-Rita Ibeawuchi Dominique Lie Mahitha Shree Anandachar Rama Pranadinata Manuela Raffatellu Soumita Das
author_sort	Ibrahim M Sayed
title	The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
title_short	The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
title_full	The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
title_fullStr	The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
title_full_unstemmed	The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
title_sort	interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/d7b9dca0753d4394bab8eb20083824c4
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The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses

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