Identification of CX3CR1(+) mononuclear phagocyte subsets involved in HIV-1 and SIV colorectal transmission

The difficulty to unambiguously identify the various subsets of mononuclear phagocytes (MNPs) of the intestinal lamina propria has hindered our understanding of the initial events occurring after mucosal exposure to HIV-1. Here, we compared the composition and function of MNP subsets at steady-state and following ex vivo and in vivo viral exposure in human and macaque colorectal tissues. Combined evaluation of CD11c, CD64, CD103, and CX3CR1 expression allowed to differentiate lamina propria MNPs subsets common to both species. Among them, CD11c(+) CX3CR1(+) cells expressing CCR5 migrated inside the epithelium following ex vivo and in vivo exposure of colonic tissue to HIV-1 or SIV. In addition, the predominant population of CX3CR1(high) macrophages present at steady-state partially shifted to CX3CR1(low) macrophages as early as three days following in vivo SIV rectal challenge of macaques. Our analysis identifies CX3CR1(+) MNPs as novel players in the early events of HIV-1 and SIV colorectal transmission.