Shifting Dynamics of Intestinal Macrophages during Simian Immunodeficiency Virus Infection in Adult Rhesus Macaques.

The intestinal tract is a primary barrier to invading pathogens and contains immune cells, including lymphocytes and macrophages. We previously reported that CD163CD206 (single-positive [SP]) interstitial macrophages of the lung are short-lived and succumb early to SIV infection. Conversely, CD163CD206 (double-positive [DP]) alveolar macrophages are long-lived, survive after SIV infection, and may contribute to the virus reservoir. This report characterizes analogous populations of macrophages in the intestinal tract of rhesus macaques () with SIV/AIDS. By flow cytometry analysis, immunofluorescence staining, and confocal microscopy, CD163CD206 DP macrophages predominated in the lamina propria of uninfected animals, compared with CD163CD206 SP macrophages, which predominated in the lamina propria in animals with SIV infection that were exhibiting AIDS. In submucosal areas, CD163CD206 DP macrophages predominated in both SIV-infected and uninfected macaques. Furthermore, BrdU-labeled CD163CD206 DP and CD163CD206 SP macrophages recently arriving in the colon, which are both presumed to be shorter-lived, were observed to localize only in the lamina propria. Conversely, longer-lived CD163CD206 DP macrophages that retained dextran at least 2 mo after in vivo administration localized exclusively in the submucosa. This suggests that CD163CD206 DP intestinal macrophages of the lamina propria were destroyed after SIV infection and replaced by immature CD163CD206 SP macrophages, whereas longer-lived CD163CD206 DP macrophages remained in the submucosa, supporting their potential role as an SIV/HIV tissue reservoir. Moreover, the DP macrophages in the submucosa, which differ from lamina propria DP macrophages, may be missed from pinch biopsy sampling, which may preclude detecting virus reservoirs for monitoring HIV cure.