Immunotyping of microglia and macrophages in the CNS during acute SIV infection: a single-cell study of rhesus macaque brains
Human immunodeficiency virus (HIV) is widely recognized for its striking impact on the immune system. Even though HIV is primarily known for the impairment of the peripheral CD4 T cells, its influence on the central nervous system (CNS) also cannot be neglected. The main immune constituents in the brain, microglia and macrophages, are the target for HIV in the brain, as well as for the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects as well as the establishment of a virus reservoir. Given the gaps in our knowledge on how these cells respond in vivo to CNS infection, we performed single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of 3 rhesus macaque with 12-day SIV infection as well as 3 uninfected controls. We identified six microglial clusters and two macrophage clusters by transcriptomic profiling. Intriguingly, there were two microglial clusters populated with the cells from infected animals. These two infection-specific clusters had significantly higher expression (p < 0.05) of MHC class I molecules, interferon-induced proteins, chemokines, and cytokines than did the other clusters. Although only a low proportion of SIV-infected cells were detected in microglia and macrophages (~0.14%), almost all the microglia and macrophages in infected animals were activated to certain extents. In addition, the clusters with higher expression of cytotoxic molecules increased their populations during the infection, suggesting their potential to cause HIV-associated neurological disorders. Overall design: 92T, 104T, 111T were non-infected control samples and other three (93T, 94T, 95T) were in acute-infected group. The rhesus macaques in the acut-infected group were infected with Simian Immunodeficiency Virus (SIV) for 12 days