Neurodegenerative phagocytes mediate synaptic stripping in Neuro-HIV.
Giovanni Di LibertoKristof EgervariMario KreutzfeldtChristian M SchürchEkkehard HewerIngrid WagnerRenaud Du PasquierDoron MerklerPublished in: Brain : a journal of neurology (2022)
Glial cell activation is a hallmark of several neurodegenerative and neuroinflammatory diseases. During HIV infection, neuroinflammation is associated with cognitive impairment, even during sustained long-term suppressive antiretroviral therapy. However, the cellular subsets contributing to neuronal damage in the CNS during HIV infection remain unclear. Using post-mortem brain samples from eight HIV patients and eight non-neurological disease controls, we identify a subset of CNS phagocytes highly enriched in LGALS3, CTSB, GPNMB and HLA-DR, a signature identified in the context of ageing and neurodegeneration. In HIV patients, the presence of this phagocyte phenotype was associated with synaptic stripping, suggesting an involvement in the pathogenesis of HIV-associated neurocognitive disorder. Taken together, our findings elucidate some of the molecular signatures adopted by CNS phagocytes in HIV-positive patients and contribute to the understanding of how HIV might pave the way to other forms of cognitive decline in ageing HIV patient populations.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- human immunodeficiency virus
- hiv aids
- men who have sex with men
- hiv infected patients
- end stage renal disease
- hiv testing
- cognitive decline
- south africa
- hepatitis c virus
- ejection fraction
- chronic kidney disease
- prognostic factors
- peritoneal dialysis
- newly diagnosed
- cognitive impairment
- blood brain barrier
- mild cognitive impairment
- gene expression
- patient reported outcomes
- inflammatory response
- stem cells
- oxidative stress
- bipolar disorder
- traumatic brain injury
- multiple sclerosis
- white matter
- single cell
- brain injury
- spinal cord injury
- lipopolysaccharide induced
- mesenchymal stem cells
- cerebral ischemia
- functional connectivity