HIV infection exacerbates ischemic brain injury through dysregulating phagocytosis and neuroinflammatory signals in macrophages/microglia via C1ql2

As the major reservoir of HIV, resident microglia and infiltrative macrophages in the brain can be aberrantly activated by HIV after stroke. However, the underlying reason driving these pathological processes in poststroke brain injury remains unclear.

Herein, with the use of ischemia mice and oxygen-glucose deprivation models, we revealed that HIV infection induced a proinflammatory phenotype and impaired the phagocytic clearance of dead/dying neurons by macrophages/microglia, which was accompanied by a marked reduction in complement C1q-like protein (C1ql) 2 in both peri-infarct macrophages/microglia and cerebrospinal fluid. Importantly, these pathological changes, with ischemia-induced neural demyelination, were strongly mitigated by the intracerebral delivery of recombinant C1ql2, which culminated in a reduced infarct volume and neurological deficits poststroke.