Mucosal IL-7 response in the gut during HIV/SIV acute infection

Carolina Moraes-Cabe (1) , Magali Rancez (1) , Bénédicte Charmeteau-De-Muylder (1) , Suzanne Figueiredo-Morgado (1) , Magali Mas (1) , Rémi Cheynier (1) , Anne Couëdel-Courteille (1, 2)

1 IC UM3 (UMR 8104 / U1016) - Institut Cochin
2 UPD7 - Université Paris Diderot - Paris 7

Background: The very early events of the mucosal immune response to HIV/SIV infection still remain poorly understood. Our previous results demonstrate that IL-7 is expressed in the gut as part of the cytokine storm that occurs during initial virus dissemination, coincidently with viral spread and associated with an increased production of chemokines, leading to immune cell homing. The aim of this work was to identify mucosal cells responsible for this early IL-7 production as well as those responding to IL-7 by chemokine production in the gut. Methods: We thus analysed separately different cell types, known to be present in the gut mucosa to find out how much they can up-regulate their IL-7 production upon inflammatory conditions or how much they are able to secrete chemokines upon IL-7 stimulation. We used epithelial and endothelial cells isolated from gut mucosa of healthy macaques, as well as human endothelial cells differentiated from circulating endothelial cell precursors. These cells were cultured with the supernatant of SIV-infected or non-infected activated PBL or stimulated by pro-inflammatory cytokines with or without IL-7. IL-7 production was measured by RT-qPCR and ELISA in the supernatant of cultured cells. CD127 expression was analysed by RT-qPCR and FACS analysis. Chemokine production was measured by RT-qPCR and MSD. Results: We demonstrated that supernatants of infected activated PBLs boosted IL-7 production by epithelial cells, contrarily to the supernatants of non-infected PBLs. These cells also up-regulated their IL-7 production when stimulated by Interferons (IFNs). Endothelial cells showed an increased expression of CD127 when stimulated by TNF or IFNs, with higher expression when co-stimulated by IL-7, suggesting an increased responsiveness of cells to the IL-7 present in the gut environment during the SIV infection driven inflammatory status. In addition, IL-7 combined to inflammatory cytokines induced higher expression of chemokines by endothelial cells, such as IP-10, IL-8 and RANTES, which are important chemo-attractive molecules for immune cells. Conclusions: This work demonstrates that IL-7 production by intestinal epithelial cells is up regulated by inflammatory signals and identifies endothelial cells as one of the chemokine-expressing cell types under IL-7 stimulation.

Domaines: Sciences du Vivant [q-bio]

Carolina Moraes-Cabe, Magali Rancez, Bénédicte Charmeteau-De-Muylder, Suzanne Figueiredo-Morgado, Magali Mas, et al.. Mucosal IL-7 response in the gut during HIV/SIV acute infection. 22nd International AIDS Conference (AIDS 2018), Jul 2018, Amsterdam, Netherlands. 2018. ⟨hal-03000417⟩