Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.

HIV causes rapid CD4+ T cell depletion in the gut mucosa, resulting in immune deficiency and defects in the intestinal epithelial barrier. Breakdown in gut barrier integrity is linked to chronic inflammation and disease progression. However, the early effects of HIV on the gut epithelium, prior to t...

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Autores principales:	Lauren A Hirao, Irina Grishina, Olivier Bourry, William K Hu, Monsicha Somrit, Sumathi Sankaran-Walters, Chris A Gaulke, Anne N Fenton, Jay A Li, Robert W Crawford, Frank Chuang, Ross Tarara, Maria L Marco, Andreas J Bäumler, Holland Cheng, Satya Dandekar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/39e65dcf61714c3bb375b0960c97f274
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spelling	oai:doaj.org-article:39e65dcf61714c3bb375b0960c97f2742021-11-25T05:46:06ZEarly mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.1553-73661553-737410.1371/journal.ppat.1004311https://doaj.org/article/39e65dcf61714c3bb375b0960c97f2742014-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25166758/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374HIV causes rapid CD4+ T cell depletion in the gut mucosa, resulting in immune deficiency and defects in the intestinal epithelial barrier. Breakdown in gut barrier integrity is linked to chronic inflammation and disease progression. However, the early effects of HIV on the gut epithelium, prior to the CD4+ T cell depletion, are not known. Further, the impact of early viral infection on mucosal responses to pathogenic and commensal microbes has not been investigated. We utilized the SIV model of AIDS to assess the earliest host-virus interactions and mechanisms of inflammation and dysfunction in the gut, prior to CD4+ T cell depletion. An intestinal loop model was used to interrogate the effects of SIV infection on gut mucosal immune sensing and response to pathogens and commensal bacteria in vivo. At 2.5 days post-SIV infection, low viral loads were detected in peripheral blood and gut mucosa without CD4+ T cell loss. However, immunohistological analysis revealed the disruption of the gut epithelium manifested by decreased expression and mislocalization of tight junction proteins. Correlating with epithelial disruption was a significant induction of IL-1β expression by Paneth cells, which were in close proximity to SIV-infected cells in the intestinal crypts. The IL-1β response preceded the induction of the antiviral interferon response. Despite the disruption of the gut epithelium, no aberrant responses to pathogenic or commensal bacteria were observed. In fact, inoculation of commensal Lactobacillus plantarum in intestinal loops led to rapid anti-inflammatory response and epithelial tight junction repair in SIV infected macaques. Thus, intestinal Paneth cells are the earliest responders to viral infection and induce gut inflammation through IL-1β signaling. Reversal of the IL-1β induced gut epithelial damage by Lactobacillus plantarum suggests synergistic host-commensal interactions during early viral infection and identify these mechanisms as potential targets for therapeutic intervention.Lauren A HiraoIrina GrishinaOlivier BourryWilliam K HuMonsicha SomritSumathi Sankaran-WaltersChris A GaulkeAnne N FentonJay A LiRobert W CrawfordFrank ChuangRoss TararaMaria L MarcoAndreas J BäumlerHolland ChengSatya DandekarPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 8, p e1004311 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Lauren A Hirao Irina Grishina Olivier Bourry William K Hu Monsicha Somrit Sumathi Sankaran-Walters Chris A Gaulke Anne N Fenton Jay A Li Robert W Crawford Frank Chuang Ross Tarara Maria L Marco Andreas J Bäumler Holland Cheng Satya Dandekar Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.
description	HIV causes rapid CD4+ T cell depletion in the gut mucosa, resulting in immune deficiency and defects in the intestinal epithelial barrier. Breakdown in gut barrier integrity is linked to chronic inflammation and disease progression. However, the early effects of HIV on the gut epithelium, prior to the CD4+ T cell depletion, are not known. Further, the impact of early viral infection on mucosal responses to pathogenic and commensal microbes has not been investigated. We utilized the SIV model of AIDS to assess the earliest host-virus interactions and mechanisms of inflammation and dysfunction in the gut, prior to CD4+ T cell depletion. An intestinal loop model was used to interrogate the effects of SIV infection on gut mucosal immune sensing and response to pathogens and commensal bacteria in vivo. At 2.5 days post-SIV infection, low viral loads were detected in peripheral blood and gut mucosa without CD4+ T cell loss. However, immunohistological analysis revealed the disruption of the gut epithelium manifested by decreased expression and mislocalization of tight junction proteins. Correlating with epithelial disruption was a significant induction of IL-1β expression by Paneth cells, which were in close proximity to SIV-infected cells in the intestinal crypts. The IL-1β response preceded the induction of the antiviral interferon response. Despite the disruption of the gut epithelium, no aberrant responses to pathogenic or commensal bacteria were observed. In fact, inoculation of commensal Lactobacillus plantarum in intestinal loops led to rapid anti-inflammatory response and epithelial tight junction repair in SIV infected macaques. Thus, intestinal Paneth cells are the earliest responders to viral infection and induce gut inflammation through IL-1β signaling. Reversal of the IL-1β induced gut epithelial damage by Lactobacillus plantarum suggests synergistic host-commensal interactions during early viral infection and identify these mechanisms as potential targets for therapeutic intervention.
format	article
author	Lauren A Hirao Irina Grishina Olivier Bourry William K Hu Monsicha Somrit Sumathi Sankaran-Walters Chris A Gaulke Anne N Fenton Jay A Li Robert W Crawford Frank Chuang Ross Tarara Maria L Marco Andreas J Bäumler Holland Cheng Satya Dandekar
author_facet	Lauren A Hirao Irina Grishina Olivier Bourry William K Hu Monsicha Somrit Sumathi Sankaran-Walters Chris A Gaulke Anne N Fenton Jay A Li Robert W Crawford Frank Chuang Ross Tarara Maria L Marco Andreas J Bäumler Holland Cheng Satya Dandekar
author_sort	Lauren A Hirao
title	Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.
title_short	Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.
title_full	Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.
title_fullStr	Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.
title_full_unstemmed	Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.
title_sort	early mucosal sensing of siv infection by paneth cells induces il-1β production and initiates gut epithelial disruption.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/39e65dcf61714c3bb375b0960c97f274
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Early mucosal sensing of SIV infection by paneth cells induces IL-1β production and initiates gut epithelial disruption.

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