Acute Simian Immunodeficiency Virus Infection Triggers Early and Transient Interleukin-7 Production in the Gut, Leading to Enhanced Local Chemokine Expression and Intestinal Immune Cell Homing

Autor: Ponte, Rosalie, Rancez, Magali, Figueiredo-Morgado, Suzanne, Dutrieux, Jacques, Fabre-Mersseman, Véronique, Charmeteau-de-Muylder, Bénédicte, Guilbert, Thomas, Routy, Jean-Pierre, Cheynier, Rémi, Couëdel-Courteille, Anne
Přispěvatelé: Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Division of Experimental Medicine [Montréal, QC, Canada] (Department of Medicine), McGill University Health Center [Montreal] (MUHC), Université Paris Diderot - Paris 7 (UPD7), This work was supported by ANRS (Agence Nationale de Recherches sur le SIDA et les Hépatites Virales), SIDACTION, INSERM, CNRS, and Paris Descartes University. The H.Grenville Smith Fellowship from the Research Institute of the McGill University Health Centre presently supports RP., Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Division of Experimental Medicine [Montréal, QC, Canada] ( Department of Medicine ), McGill University Health Center [Montreal, Canada] ( MUHC ), Université Paris Diderot - Paris 7 ( UPD7 ), Bos, Mireille
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Frontiers in Cellular and Infection Microbiology
Frontiers in Cellular and Infection Microbiology, Frontiers, 2017, 8, pp.588. ⟨10.3389/fimmu.2017.00588⟩
Frontiers in Immunology
Frontiers in Cellular and Infection Microbiology, Frontiers Media, 2017, 8, pp.588. 〈10.3389/fimmu.2017.00588〉
Frontiers in Cellular and Infection Microbiology, 2017, 8, pp.588. ⟨10.3389/fimmu.2017.00588⟩
ISSN: 2235-2988
Popis: International audience; The intestinal barrier, one of the first targets of HIV/simian immunodeficiency virus (SIV) is subjected to major physiological changes during acute infection. Having previously shown that pharmaceutical injection of interleukin-7 (IL-7) triggers chemokine expression in many organs leading to massive T-cell homing, in particular to the intestine, we here explored mucosal IL-7 expression as part of the cytokine storm occurring during the acute phase of SIV infection in rhesus macaques. Quantifying both mRNA and protein in tissues, we demonstrated a transient increase of IL-7 expression in the small intestine of SIV-infected rhesus macaques, starting with local detection of the virus by day 3 of infection. We also observed increased transcription levels of several chemokines in the small intestine. In infected macaques, ileal IL-7 expression correlated with the transcription of four of these chemokines. Among these chemokines, the macrophage and/or T-cell attractant chemokines CCL4, CCL25, and CCL28 also demonstrated increased transcription in uninfected IL-7-treated monkeys. Through immunohistofluorescence staining and image analysis, we observed increased CD8+ T-cell numbers and stable CD4+ T-cell counts in the infected lamina propria (LP) during hyperacute infection. Concomitantly, circulating CCR9+beta7+ CD4+ and CD8+ T-cells dropped during acute infection, suggesting augmented intestinal homing of gut-imprinted T-cells. Finally, CD4+ macrophages transiently decreased in the submucosa and concentrated in the LP during the first days of infection. Overall, our study identifies IL-7 as a danger signal in the small intestine of Chinese rhesus macaques in response to acute SIV infection. Through stimulation of local chemokine expressions, this overexpression of IL-7 triggers immune cell recruitment to the gut. These findings suggest a role for IL-7 in the initiation of early mucosal immune responses to SIV and HIV infections. However, IL-7 triggered CD4+ T-cells and macrophages localization at viral replication sites could also participate to viral spread and establishment of viral reservoirs.
Databáze: OpenAIRE
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