Conventional Dendritic Cells and Slan+ Monocytes During HIV-2 Infection.

Marco Iannetta,Diane Descamps,Sophie Matheron,Suzanne Figueiredo,Rodolphe Thiébaut,Assia Samri,Muriel Andrieu,Anne Hosmalin,Laura Vaton,Bénédicte Charmeteau-De Muylder,Charlotte Charpentier,Lene Vimeux,David Glohi,Karine Bailly,Etienne X Hatton,Brigitte Autran,Stéphane Isnard,Jean-Baptiste Guillerme,Sonia Amraoui,Nathalie Chaghil,Françoise Brun‐Vézinet ,Jennifer A Manuzak ,Rémi Cheynier ,Mathilde Notin

doi:10.3389/fimmu.2020.01658

Abstract

HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14++CD16+ monocytes were found to accumulate and CD11c+ conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank healthy donors (HD). We studied more precisely classical monocytes; CD16+ inflammatory (intermediate, non-classical and slan+ monocytes, known to accumulate during viremic HIV-1 infection); cDC1, important for cross-presentation, and cDC2, both depleted during HIV-1 infection. We analyzed by flow cytometry these PBMC subsets from Paris area residents: 29 asymptomatic, untreated PLWHIV-2 from the IMMUNOVIR-2 study, part of the ANRS-CO5 HIV-2 cohort: 19 long-term non-progressors (LTNP; infection ≥8 years, undetectable viral load, stable CD4 counts≥500/μL; 17 of West-African origin -WA), and 10 non-LTNP (P; progressive infection; 9 WA); and 30 age-and sex-matched controls: 16 blood bank HD with unknown geographical origin, and 10 HD of WA origin (GeoHD). We measured plasma bacterial translocation markers by ELISA. Non-classical monocyte counts were higher in GeoHD than in HD (54 vs. 32 cells/μL, p = 0.0002). Slan+ monocyte counts were twice as high in GeoHD than in HD (WA: 28 vs. 13 cells/μL, p = 0.0002). Thus cell counts were compared only between participants of WA origin. They were similar in LTNP, P and GeoHD, indicating that there were no HIV-2 related differences. cDC counts did not show major differences between the groups. Interestingly, inflammatory monocyte counts correlated with plasma sCD14 and LBP only in PLWHIV-2, especially LTNP, and not in GeoHD. In conclusion, in LTNP PLWHIV-2, inflammatory monocyte counts correlated with LBP or sCD14 plasma levels, indicating a potential innate immune response to subclinical bacterial translocation. As GeoHD had higher inflammatory monocyte counts than HD, our data also show that specific controls are important to refine innate immunity studies.

Highlights

HIV-2 infection [1] is mostly prevalent in West Africa, and in populations emigrated from West Africa to Portugal and France [1,2,3]
Ageand sex- matched with the HIV-2+ participants, 16 from the French blood bank [Etablissement Français du Sang (EFS)] (HD), and 10 matched with most HIV2+ participants for their West-African origin (GeoHD), were enrolled as control groups
In untreated HIV-2 infected participants from the IMMUNOVIR-2 study, the blood counts of subpopulations of monocytes or conventional dendritic cells (cDC) that were shown previously to be affected in HIV-1 infected individuals

Summary

Introduction

HIV-2 infection [1] is mostly prevalent in West Africa, and in populations emigrated from West Africa to Portugal and France [1,2,3]. Circulating non-classical monocyte (CD14+CD16+) counts are higher in both asymptomatic chronically HIV-1-infected people with high viremia and in people developing AIDS than in people with low viremia or in uninfected donors [8, 9]. They were found to be more permissive to HIV-1 infection in vivo and in vitro than other monocytes and to correlate with plasma sCD14 levels and microbial translocation [10, 11]. They are known to be present in the lesions of major inflammatory chronic diseases like Crohn’s

Methods

Results

Conclusion