Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

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CD14+CD16+ monocyte transmigration across the blood-brain barrier is associated with HIV-NCI despite viral suppression.

Abstract

HIV-associated neurocognitive impairment (HIV-NCI) affects 15%-50% of people with HIV (PWH), despite viral suppression with antiretroviral therapy (ART). HIV neuropathogenesis is mediated, in part, by transmigration of infected CD14+CD16+ monocytes across the blood-brain barrier (BBB) into the central nervous system (CNS). In the CNS, CD14+CD16+ monocytes contribute to infection and activation of parenchymal cells, resulting in production of neurotoxic viral and host factors that cause neuronal damage. Mechanisms by which CD14+CD16+ monocytes contribute to HIV-NCI have not been characterized in a study population of PWH on ART without contribution from confounders that affect cognition (e.g., substance use, hepatitis C virus coinfection). We assessed cognitive function, PBMC transmigration across the BBB, and neuronal health markers in a well-defined cohort of 56 PWH on ART using stringent criteria to eliminate confounding factors. We demonstrated that PWH on ART with HIV-NCI have significantly increased transmigration of their CD14+CD16+ monocytes across the BBB compared with those with normal cognition. We showed that hypertension and diabetes may be effect modifiers on the association between CD14+CD16+ monocyte transmigration and cognition. This study underscored the persistent role of CD14+CD16+ monocytes in HIV-NCI, even in PWH with viral suppression, suggesting them as potential targets for therapeutic interventions.

Authors: Veksler V, Leon-Rivera R, Fleysher L, Gonzalez J, Lopez JA, Rubin LH, Morgello S, Berman JW,
Journal: JCI Insight;2024 Sep 10;9(17):e179855. doi:10.1172/jci.insight.179855
Year: 2024
PubMed: PMID: 39253970 (Go to PubMed)