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Updated: Jun 28, 2025
A Thin-skull Window Technique for Chronic Two-photon In vivo Imaging of Murine Microglia in Models of Neuroinflammation
Published on: September 19, 2010
Microglia and macrophages alterations in the CNS during acute SIV infection: a single-cell analysis in rhesus
Xiaoke Xu1, Meng Niu1, Benjamin G Lamberty1
1Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Abstract:
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, as well as for the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects and the establishment of 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 population of homeostatic and preactivated microglia 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: CD14lowCD16hi and CD14hiCD16low CAMs. Interestingly, during acute SIV infection, the dominant CAM population changed to one with an inflammatory phenotype. Notably, 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.
Insights
Simian immunodeficiency virus (SIV) infection alters brain myeloid cells, increasing inflammatory microglia and macrophages. These changes suggest potential links to neuroinflammation and neurocognitive disorders in acute central nervous system infection.
Area of Science:
- Neurovirology
- Immunology
- Central Nervous System (CNS) Research
Background:
- Human Immunodeficiency Virus (HIV) impacts the CNS, with microglia and CNS-associated macrophages (CAMs) being primary targets.
- Understanding the in vivo response of these myeloid cells to acute CNS infection is crucial for addressing neurological complications.
- Simian immunodeficiency virus (SIV) in nonhuman primates serves as a relevant model for studying HIV's CNS effects.
Conclusions:
- Acute SIV infection induces significant alterations in brain myeloid cell populations, characterized by increased inflammatory responses.
- Microglia and CAMs play critical roles in the early defense against SIV in the CNS.
- The observed molecular changes, including upregulation of senescence and neurodegeneration-associated genes, highlight potential mechanisms underlying SIV-related neurological disorders.
- This study provides novel insights into the complex interplay between viral CNS infection and innate immunity.
