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<p>The incidence of human immunodeficiency virus (HIV)-infected individuals is greater, and outcomes are worse following cerebral stroke, despite widespread access to antiretroviral therapy. 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. Notably, delivering recombinant C1ql2 in the presence of gavage antiretroviral drug Biktarvy further promoted functional recovery and rescued tissue loss following chronic ischemia in HIV-bearing mice, underscoring its potential therapeutic relevance. Collectively, these findings reveal a previously unrecognized C1ql2-dependent mechanism through which HIV infection impairs poststroke repair, which highlights C1ql2 restoration as a promising neuroprotective strategy for HIV-infected stroke patients.</p><p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Fan Bu,
  • Xiude Qin,
  • Longsheng Xu,
  • Yiyao Hu,
  • Zhaohui Dang,
  • Xi Xiao,
  • Lingyun Ge,
  • Liqin Sun,
  • Zicheng Zhang,
  • Hui Wu,
  • Jiaye Liu

摘要

The incidence of human immunodeficiency virus (HIV)-infected individuals is greater, and outcomes are worse following cerebral stroke, despite widespread access to antiretroviral therapy. 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. Notably, delivering recombinant C1ql2 in the presence of gavage antiretroviral drug Biktarvy further promoted functional recovery and rescued tissue loss following chronic ischemia in HIV-bearing mice, underscoring its potential therapeutic relevance. Collectively, these findings reveal a previously unrecognized C1ql2-dependent mechanism through which HIV infection impairs poststroke repair, which highlights C1ql2 restoration as a promising neuroprotective strategy for HIV-infected stroke patients.