Diet, commensal microbiota-derived extracellular vesicles, and host immunity.

The gut microbiota has co-evolved with its host, and commensal bacteria can influence both the host's immune development and function. Recently, a role has emerged for bacterial extracellular vesicles (BEVs) as potent immune modulators. BEVs are nanosized membrane vesicles produced by all bacteria, possessing the membrane characteristics of the originating bacterium and carrying an internal cargo that may include nucleic acid, proteins, lipids, and metabolites. Thus, BEVs possess multiple avenues for regulating immune processes, and have been implicated in allergic, autoimmune, and metabolic diseases. BEVs are biodistributed locally in the gut, and also systemically, and thus have the potential to affect both the local and systemic immune responses. The production of gut microbiota-derived BEVs is regulated by host factors such as diet and antibiotic usage. Specifically, all aspects of nutrition, including macronutrients (protein, carbohydrates, and fat), micronutrients (vitamins and minerals), and food additives (the antimicrobial sodium benzoate), can regulate BEV production. This review summarizes current knowledge of the powerful links between nutrition, antibiotics, gut microbiota-derived BEV, and their effects on immunity and disease development. It highlights the potential of targeting or utilizing gut microbiota-derived BEV as a therapeutic intervention.

NK cell profiling in West Nile virus encephalitis reveals potential metabolic basis for functional inhibition.

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.