Iannetta Marco, Isnard Stéphane, Manuzak Jennifer, Guillerme Jean-Baptiste, Notin Mathilde, Bailly Karine, Andrieu Muriel, Amraoui Sonia, Vimeux Lene, Figueiredo Suzanne, Charmeteau-de Muylder Bénédicte, Vaton Laura, Hatton Etienne X, Samri Assia, Autran Brigitte, Thiébaut Rodolphe, Chaghil Nathalie, Glohi David, Charpentier Charlotte, Descamps Diane, Brun-Vézinet Françoise, Matheron Sophie, Cheynier Remi, Hosmalin Anne
Université de Paris, Institut Cochin, CNRS, INSERM, Paris, France.
Sorbonne Université, Inserm 1135, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France.
Front Immunol. 2020 Aug 13;11:1658. doi: 10.3389/fimmu.2020.01658. eCollection 2020.
HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14CD16 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, = 0.0002). Slan monocyte counts were twice as high in GeoHD than in HD (WA: 28 vs. 13 cells/μL, = 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.
与HIV-1感染相比，HIV-2感染的特点是病毒血症水平低且疾病进展缓慢。在一个葡萄牙的HIV-2感染者（PLWHIV-2）队列中，发现循环中的CD14CD16单核细胞会积聚，而CD11c传统树突状细胞（cDC）会减少，与之相比的是血库健康供者（HD）。我们更精确地研究了经典单核细胞；CD16炎性单核细胞（中间型、非经典型和Slan单核细胞，已知在病毒血症性HIV-1感染期间会积聚）；对交叉呈递很重要的cDC1，以及在HIV-1感染期间均会减少的cDC2。我们通过流式细胞术分析了来自巴黎地区居民的这些外周血单核细胞亚群：来自IMMUNOVIR-2研究（ANRS-CO5 HIV-2队列的一部分）的29名无症状、未接受治疗的PLWHIV-2感染者：19名长期不进展者（LTNP；感染≥8年，病毒载量不可检测，稳定的CD4细胞计数≥500/μL；其中17名来自西非 -WA），以及10名非LTNP（P；进展性感染；9名来自WA）；还有30名年龄和性别匹配的对照：16名血库HD，地理来源不明，以及10名来自WA的HD（GeoHD）。我们通过酶联免疫吸附测定法测量血浆细菌易位标志物。GeoHD中的非经典单核细胞计数高于HD（54对32个细胞/μL，P = 0.0002）。GeoHD中的Slan单核细胞计数是HD中的两倍（WA：28对13个细胞/μL，P = 0.0002）。因此，仅在来自WA的参与者之间比较细胞计数。它们在LTNP、P和GeoHD中相似，表明不存在与HIV-2相关的差异。各组之间的cDC计数没有显示出主要差异。有趣的是，炎性单核细胞计数仅在PLWHIV-2感染者中，尤其是LTNP中，与血浆sCD14和LBP相关，而在GeoHD中则不然。总之，在LTNP PLWHIV-2感染者中，炎性单核细胞计数与LBP或sCD14血浆水平相关，表明对亚临床细菌易位可能存在先天性免疫反应。由于GeoHD的炎性单核细胞计数高于HD，我们的数据还表明特定的对照对于完善先天性免疫研究很重要。
