Advancing basic and translational research to deepen understanding of the molecular immune-mediated mechanisms regulating long-term persistence of HIV-1 in microglia in the adult human brain

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Thomas Boucher¹  Shijun Liang¹  Amanda M. Brown¹ 

[1] Department of Neurology, Johns Hopkins University School of Medicine

关键词: monocytes;    innate immunity;    inflammation;    central nervous system;    bone marrow progenitors;    myeloid;    phagocytosis;   

DOI  :  10.1002/JLB.1MR0422-620R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Knowledge about the diversity microglia (MG) type and function in the rodent andhuman brain has advanced significantly in the last few years. Nevertheless, we haveknown for 40 years that MG, monocytes, and macrophages in the brain play crucialroles in the pathogenesis of the HIV-1 in all tissues. HIV enters and spreads in thebrain early, long before the initiation of antiviral therapy. As a result, many people withHIV continue to experience neurologic and neuropsychiatric comorbid conditions collectively known as HIV-associated neurocognitive disorder (HAND). HIV pathogenicsequelae in the CNS pose a challenge for cure strategies. Detailed understanding at amechanistic level of how low-level and latent HIV-1 infection in MG negatively impactsneuroglial function has remained somewhat elusive. Direct rigorous in vivo experimental validation that the virus can integrate intoMG and assume a latent but reactivatablestate has remained constrained. However, there is much excitement that human invitro models for MG can now help close the gap. This review will provide a brief background to place the role ofMG in the ongoing neurologic complications of HIV infectionof the CNS, then focus on the use and refinement of human postmitotic monocytederived MG-like cells and how they are being applied to advance research on HIVpersistence and proinflammatory signaling in the CNS. Critically, an understandingof myeloid plasticity and heterogeneity and rigorous attention to all aspects of cellhandling is essential for reproducibility.

【 授权许可】

CC BY