TRPV1 activation in human Langerhans cells and T cells inhibits mucosal HIV-1 infection via CGRP-dependent and independent mechanisms - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2023

TRPV1 activation in human Langerhans cells and T cells inhibits mucosal HIV-1 infection via CGRP-dependent and independent mechanisms

Jammy Mariotton
  • Fonction : Auteur
Emmanuel Cohen
  • Fonction : Auteur
Aiwei Zhu
  • Fonction : Auteur
Cédric Auffray
Caio César Barbosa Bomfim
Morgane Bomsel
Yonatan Ganor
  • Fonction : Auteur

Résumé

Upon its mucosal transmission, HIV type 1 (HIV-1) rapidly targets genital antigen-presenting Langerhans cells (LCs), which subsequently transfer infectious virus to CD4 + T cells. We previously described an inhibitory neuroimmune cross talk, whereby calcitonin gene-related peptide (CGRP), a neuropeptide secreted by peripheral pain-sensing nociceptor neurons innervating all mucosal epithelia and associating with LCs, strongly inhibits HIV-1 transfer. As nociceptors secret CGRP following the activation of their Ca 2+ ion channel transient receptor potential vanilloid 1 (TRPV1), and as we reported that LCs secret low levels of CGRP, we investigated whether LCs express functional TRPV1. We found that human LCs expressed mRNA and protein of TRPV1, which was functional and induced Ca 2+ influx following activation with TRPV1 agonists, including capsaicin (CP). The treatment of LCs with TRPV1 agonists also increased CGRP secretion, reaching its anti-HIV-1 inhibitory concentrations. Accordingly, CP pretreatment significantly inhibited LCs-mediated HIV-1 transfer to CD4 + T cells, which was abrogated by both TRPV1 and CGRP receptor antagonists. Like CGRP, CP-induced inhibition of HIV-1 transfer was mediated via increased CCL3 secretion and HIV-1 degradation. CP also inhibited direct CD4 + T cells HIV-1 infection, but in CGRP-independent manners. Finally, pretreatment of inner foreskin tissue explants with CP markedly increased CGRP and CCL3 secretion, and upon subsequent polarized exposure to HIV-1, inhibited an increase in LC–T cell conjugate formation and consequently T cell infection. Our results reveal that TRPV1 activation in human LCs and CD4 + T cells inhibits mucosal HIV-1 infection, via CGRP-dependent/independent mechanisms. Formulations containing TRPV1 agonists, already approved for pain relief, could hence be useful against HIV-1.
Fichier principal
Vignette du fichier
2023 Mariotton PNAS.pdf (2.18 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04254352 , version 1 (23-10-2023)

Identifiants

Citer

Jammy Mariotton, Emmanuel Cohen, Aiwei Zhu, Cédric Auffray, Caio César Barbosa Bomfim, et al.. TRPV1 activation in human Langerhans cells and T cells inhibits mucosal HIV-1 infection via CGRP-dependent and independent mechanisms. Proceedings of the National Academy of Sciences of the United States of America, 2023, 120 (22), ⟨10.1073/pnas.2302509120⟩. ⟨hal-04254352⟩

Collections

CNRS UP-SANTE
4 Consultations
8 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More