Put them to bed, and “do not disturb” brain microglia in SIV infection

In the current issue of The Journal of Leukocyte Biology, Trease and colleagues have presented a unique study with a perspective on the fluidity of the status of brain myeloid cell sub‐populations (microglia and macrophages) within the SIV‐infected brain, and the implications for the cognitive health of people with HIV (PWH). Those implications for more fully understanding the role of myeloid cells in the pathogenesis of HIV‐associated neurocognitive disorders (HAND) are indeed significant. Their study attempts to capture the state of brain myeloid cells in combination ART (cART)‐suppressed, SIV‐infected rhesus macaques, through analyses of myeloid cells isolated from whole‐brain hemisphere preparations, using scRNA seq, IPA and bioinformatics. The goal was to profile the transcriptomic pattern of myeloid homeostasis during virus suppression and compare that profile to those of resting, uninfected microglia and SIV‐infected microglia in states of uncontrolled infection. The later includes active infection in non‐encephalitic and encephalitic states, the precursor and end‐stages of SIV/HIV infection of the brain, which are relevant in untreated individuals. The state of virus suppression represents the status of PLWH on suppressive cART, which is of particular interest. The homeostatic state of microglia/macrophages under viral suppression currently dominates discussions dealing with treated patient populations, which emphasizes the importance of this study. Defining the differences in the homeostatic state might identify the neuropathogenic potential of microglia to induce brain injury even without active SIV replication to reveal new therapeutic targets.