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

Abstract

The intestinal tract is a primary barrier to invading pathogens and contains immune cells, including lymphocytes and macrophages. We previously reported that CD163 + CD206 2 (single-positive [SP]) interstitial macrophages of the lung are short-lived and succumb early to SIV infection. Conversely, CD163 + CD206 + (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 (Macaca mulatta) with SIV/AIDS. By flow cytometry analysis, immunofluorescence staining, and confocal microscopy, CD163 + CD206 + DP macrophages predominated in the lamina propria of uninfected animals, compared with CD163 + CD206 2 SP macrophages, which predominated in the lamina propria in animals with SIV infection that were exhibiting AIDS. In submucosal areas, CD163 + CD206 + DP macrophages predominated in both SIV-infected and uninfected macaques. Furthermore, BrdU-labeled CD163 + CD206 + DP and CD163 + CD206 2 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 CD163 + CD206 + DP macrophages that retained dextran at least 2 mo after in vivo administration localized exclusively in the submucosa. This suggests that CD163 + CD206 + DP intestinal macrophages of the lamina propria were destroyed after SIV infection and replaced by immature CD163 + CD206 2 SP macrophages, whereas longer-lived CD163 + CD206 + 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.

Immune Profile of the Normal Maternal-Fetal Interface in Rhesus Macaques and Its Alteration Following Zika Virus Infection

“…CD14+ CD163+ CD206– myeloid cells were found in PBMC and decidua at 54.1 ± 25.8% and 18.3 ± 12.8% respectively of myeloid HLA-DR+ expressing cells ( Figure 2D ). These cells are a mix of classical and intermediate monocytes in the PBMC and recently infiltrated monocytes and macrophages in tissues ( 39 , 40 ). CD14+ CD163– CD206– cells were significantly increased in the decidua compared to PBMC ( Figure 2D ).…”

The Role of Intestinal Macrophages in Gastrointestinal Homeostasis: Heterogeneity and Implications in Disease

“…CD163 + CD206 + (double-positive) macrophages within the lamina propria are outnumbered by short-lived CD163 + CD206 - (single-positive) macrophages upon SIV infection. 128 This shift is owing to the swift targeting and killing of double-positive macrophages during SIV infection and their subsequent constitutive replenishment by the single-positive, short-lived macrophages (derived from recruited monocytes). Within the submucosa, in contrast with the lamina propria, double-positive macrophages survive longer, meaning that they potentially contribute to the SIV reservoir.…”

“…Within the submucosa, in contrast with the lamina propria, double-positive macrophages survive longer, meaning that they potentially contribute to the SIV reservoir. 128 Change of surface marker expression on intestinal macrophages therefore is crucial for detecting virus reservoir in monitoring the progression of HIV infection.…”

Laminin Isoforms in Human Dental Pulp: Lymphatic Vessels Express Laminin-332, and Schwann Cell–Associated Laminin-211 Modulates CD163 Expression of M2-like Macrophages

“…The current findings indicated phenotypically different M2like macrophage subsets; CD206 1 CD163 1 double-positive macrophages were predominantly detected in healthy dental pulp, whereas CD206 À CD163 1 single-positive macrophages were significantly increased in active carious lesions. The two subsets of macrophages have been reported in other animal tissues (34). CD206 1 CD163 1 double-positive macrophages are longlived and predominant in healthy uninfected tissues; in contrast, CD206 À CD163 1 single-positive macrophages are presumed to migrate from the blood and persist for short periods of time (34).…”