Identification of macaque dendritic cell precursors in blood and tissue reveals their dysregulation in early SIV infection.

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. [Display omitted] • Identification of human pre-DC equivalent in macaques • Pre-DCs accumulate in the lymph node from early SIV infection • IL-12p40 production capacity of lymph node pre-DCs is attenuated in SIV infection • T cell activation in HIV controllers correlates with pre-DC costimulatory markers Gardet et al. define the human equivalent of dendritic cell precursors (pre-DCs) in a monkey model of HIV infection to demonstrate their accumulation in lymph nodes but without activating properly. This insight provides a better understanding of how HIV interferes with the immune response in humans. [ABSTRACT FROM AUTHOR]