Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), 92265 Fontenay-aux-Roses, France.
Paris-Saclay University Hospital Group, Assistance Publique Hôpitaux de Paris, Department of Internal Medicine and Clinical Immunology, Bicêtre Hospital, le Kremlin-Bicêtre, France; Centre de Recherche en Épidémiologie et Santé des Populations (CESP), INSERM U1018, University Paris Saclay, Paris, France.
Cell Rep. 2024 Apr 23;43(4):113994. doi: 10.1016/j.celrep.2024.113994. Epub 2024 Mar 25.
Distinct dendritic cell (DC) subsets play important roles in shaping immune responses. Circulating DC precursors (pre-DCs) are more susceptible to HIV infection in vitro, which may explain the inefficiency of immune responses against HIV. However, the interplay between HIV and pre-DC is not defined in vivo. We identify human pre-DC equivalents in the cynomolgus macaque and then analyze their dynamics during simian immunodeficiency virus (SIV) infection to illustrate a sharp decrease of blood pre-DCs in early SIV infection and accumulation in lymph nodes (LNs), where they neglect to upregulate CD83/CD86 or MHC-II. Additionally, SIV infection attenuates the capacity of stimulated LN pre-DCs to produce IL-12p40. Analysis of HIV cohorts provides correlation between costimulatory molecule expression on pre-DCs and T cell activation in spontaneous HIV controllers. These findings pinpoint certain dynamics and functional changes of pre-DCs during SIV infection, providing a deeper understanding of immune dysregulation mechanisms elicited in people living with HIV.
不同的树突状细胞（DC）亚群在塑造免疫反应中发挥重要作用。循环树突状细胞前体（pre-DC）在体外更容易感染 HIV，这可能解释了针对 HIV 的免疫反应效率低下的原因。然而，HIV 和 pre-DC 之间的相互作用在体内尚未确定。我们在食蟹猴中鉴定出人类 pre-DC 等效物，然后分析它们在猴免疫缺陷病毒（SIV）感染期间的动态，以说明在早期 SIV 感染期间血液 pre-DC 的急剧减少，并在淋巴结（LN）中积累，在那里它们未能上调 CD83/CD86 或 MHC-II。此外，SIV 感染会减弱刺激的 LN pre-DC 产生 IL-12p40 的能力。对 HIV 队列的分析提供了 pre-DC 上共刺激分子表达与自发 HIV 控制器中 T 细胞激活之间的相关性。这些发现指出了 SIV 感染期间 pre-DC 的某些动力学和功能变化，为理解 HIV 感染者中引发的免疫失调机制提供了更深入的了解。
