NK cell profiling in West Nile virus encephalitis reveals potential metabolic basis for functional inhibition.
Alanna G SpiteriClaire L WishartGabriela V PingetShivam K PurohitLaurence MaciaNicholas Jonathan Cole KingPaula NiewoldPublished in: Immunology and cell biology (2024)
Natural killer (NK) cells are cytotoxic lymphocytes important for viral defense. West Nile virus (WNV) infection of the central nervous system (CNS) causes marked recruitment of bone marrow (BM)-derived monocytes, T cells and NK cells, resulting in severe neuroinflammation and brain damage. Despite substantial numbers of NK cells in the CNS, their function and phenotype remain largely unexplored. Here, we demonstrate that NK cells mature from the BM to the brain, upregulate inhibitory receptors and show reduced cytokine production and degranulation, likely due to the increased expression of the inhibitory NK cell molecule, MHC-I. Intriguingly, this correlated with a reduction in metabolism associated with cytotoxicity in brain-infiltrating NK cells. Importantly, the degranulation and killing capability were restored in NK cells isolated from WNV-infected tissue, suggesting that WNV-induced NK cell inhibition occurs in the CNS. Overall, this work identifies a potential link between MHC-I inhibition of NK cells and metabolic reduction of their cytotoxicity during infection.
Keyphrases
- nk cells
- bone marrow
- resting state
- white matter
- blood brain barrier
- cerebral ischemia
- oxidative stress
- poor prognosis
- functional connectivity
- traumatic brain injury
- sars cov
- mesenchymal stem cells
- peripheral blood
- dendritic cells
- early onset
- immune response
- cerebrospinal fluid
- endothelial cells
- cognitive impairment
- brain injury
- inflammatory response
- long non coding rna
- diabetic rats
- stress induced