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Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques
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Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques
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Journal Article
Microglia and macrophages alterations in the CNS during acute SIV infection: A single-cell analysis in rhesus macaques
2024
Overview
Human Immunodeficiency Virus (HIV) is widely acknowledged for its profound impact on the immune system. Although HIV primarily affects peripheral CD4 T cells, its influence on the central nervous system (CNS) cannot be overlooked. Within the brain, microglia and CNS-associated macrophages (CAMs) serve as the primary targets for HIV and the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects and establish a viral reservoir. Given the gaps in our understanding of how these cells respond
in vivo
to acute CNS infection, we conducted single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of three rhesus macaques 12 days after SIV infection, along with three uninfected controls. Our analysis revealed six distinct microglial clusters including homeostatic microglia, preactivated microglia, and activated microglia expressing high levels of inflammatory and disease-related molecules. In response to acute SIV infection, the homeostatic and preactivated microglia population decreased, while the activated and disease-related microglia increased. All microglial clusters exhibited upregulation of MHC class I molecules and interferon-related genes, indicating their crucial roles in defending against SIV during the acute phase. All microglia clusters also upregulated genes linked to cellular senescence. Additionally, we identified two distinct CAM populations: CD14
low
CD16
hi
and CD14
hi
CD16
low
CAMs. Interestingly, during acute SIV infection, the dominant CAM population changed to one with an inflammatory phenotype. Specific upregulated genes within one microglia and one macrophage cluster were associated with neurodegenerative pathways, suggesting potential links to neurocognitive disorders. This research sheds light on the intricate interactions between viral infection, innate immune responses, and the CNS, providing valuable insights for future investigations.
Publisher
Public Library of Science
Subject
Acquired immune deficiency syndrome
/ AIDS
/ Animals
/ Brain
/ Cells
/ Central Nervous System - immunology
/ Central Nervous System - virology
/ Clusters
/ Genes
/ HIV
/ Human immunodeficiency virus
/ Major histocompatibility complex
/ Medicine and Health Sciences
/ Simian Acquired Immunodeficiency Syndrome - immunology
/ Simian Acquired Immunodeficiency Syndrome - virology
/ Simian immunodeficiency virus
/ Simian Immunodeficiency Virus - immunology
/ Viruses
