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Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission

Upon its mucosal entry, human immunodeficiency virus type 1 (HIV-1) is internalized by Langerhans cells (LCs) in stratified epithelia and transferred locally to T cells. In such epithelia, LCs are in direct contact with peripheral neurons secreting calcitonin gene–related peptide (CGRP). Although CG...

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Autores principales: Ganor, Yonatan, Drillet-Dangeard, Anne-Sophie, Lopalco, Lucia, Tudor, Daniela, Tambussi, Giuseppe, Delongchamps, Nicolas Barry, Zerbib, Marc, Bomsel, Morgane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804954/
https://www.ncbi.nlm.nih.gov/pubmed/24081951
http://dx.doi.org/10.1084/jem.20122349
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author Ganor, Yonatan
Drillet-Dangeard, Anne-Sophie
Lopalco, Lucia
Tudor, Daniela
Tambussi, Giuseppe
Delongchamps, Nicolas Barry
Zerbib, Marc
Bomsel, Morgane
author_facet Ganor, Yonatan
Drillet-Dangeard, Anne-Sophie
Lopalco, Lucia
Tudor, Daniela
Tambussi, Giuseppe
Delongchamps, Nicolas Barry
Zerbib, Marc
Bomsel, Morgane
author_sort Ganor, Yonatan
collection PubMed
description Upon its mucosal entry, human immunodeficiency virus type 1 (HIV-1) is internalized by Langerhans cells (LCs) in stratified epithelia and transferred locally to T cells. In such epithelia, LCs are in direct contact with peripheral neurons secreting calcitonin gene–related peptide (CGRP). Although CGRP has immunomodulatory effects on LC functions, its potential influence on the interactions between LCs and HIV-1 is unknown. We show that CGRP acts via its receptor expressed by LCs and interferes with multiple steps of LC-mediated HIV-1 transmission. CGRP increases langerin expression, decreases selected integrins, and activates NF-κB, resulting in decreased HIV-1 intracellular content, limited formation of LC–T cell conjugates, and elevated secretion of the CCR5-binding chemokine CCL3/MIP-1α. These mechanisms cooperate to efficiently inhibit HIV-1 transfer from LCs to T cells and T cell infection. In vivo, HIV-1 infection decreases CGRP plasma levels in both vaginally SHIV-challenged macaques and HIV-1–infected individuals. CGRP plasma levels return to baseline after highly active antiretroviral therapy. Our results reveal a novel path by which a peripheral neuropeptide acts at the molecular and cellular levels to limit mucosal HIV-1 transmission and suggest that CGRP receptor agonists might be used therapeutically against HIV-1.
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spelling pubmed-38049542014-04-21 Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission Ganor, Yonatan Drillet-Dangeard, Anne-Sophie Lopalco, Lucia Tudor, Daniela Tambussi, Giuseppe Delongchamps, Nicolas Barry Zerbib, Marc Bomsel, Morgane J Exp Med Brief Definitive Report Upon its mucosal entry, human immunodeficiency virus type 1 (HIV-1) is internalized by Langerhans cells (LCs) in stratified epithelia and transferred locally to T cells. In such epithelia, LCs are in direct contact with peripheral neurons secreting calcitonin gene–related peptide (CGRP). Although CGRP has immunomodulatory effects on LC functions, its potential influence on the interactions between LCs and HIV-1 is unknown. We show that CGRP acts via its receptor expressed by LCs and interferes with multiple steps of LC-mediated HIV-1 transmission. CGRP increases langerin expression, decreases selected integrins, and activates NF-κB, resulting in decreased HIV-1 intracellular content, limited formation of LC–T cell conjugates, and elevated secretion of the CCR5-binding chemokine CCL3/MIP-1α. These mechanisms cooperate to efficiently inhibit HIV-1 transfer from LCs to T cells and T cell infection. In vivo, HIV-1 infection decreases CGRP plasma levels in both vaginally SHIV-challenged macaques and HIV-1–infected individuals. CGRP plasma levels return to baseline after highly active antiretroviral therapy. Our results reveal a novel path by which a peripheral neuropeptide acts at the molecular and cellular levels to limit mucosal HIV-1 transmission and suggest that CGRP receptor agonists might be used therapeutically against HIV-1. The Rockefeller University Press 2013-10-21 /pmc/articles/PMC3804954/ /pubmed/24081951 http://dx.doi.org/10.1084/jem.20122349 Text en © 2013 Ganor et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Ganor, Yonatan
Drillet-Dangeard, Anne-Sophie
Lopalco, Lucia
Tudor, Daniela
Tambussi, Giuseppe
Delongchamps, Nicolas Barry
Zerbib, Marc
Bomsel, Morgane
Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission
title Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission
title_full Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission
title_fullStr Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission
title_full_unstemmed Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission
title_short Calcitonin gene–related peptide inhibits Langerhans cell–mediated HIV-1 transmission
title_sort calcitonin gene–related peptide inhibits langerhans cell–mediated hiv-1 transmission
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804954/
https://www.ncbi.nlm.nih.gov/pubmed/24081951
http://dx.doi.org/10.1084/jem.20122349
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