Abstract
BackgroundHIV infection induces inflammaging and chronic immune activation (IA), which are negatively associated with protective humoral immunity. Similar to HIV, aging is also associated with increased inflammaging and IA. The metabolic requirements of B cell responses in HIV infected (HIV+) individuals are not known, although metabolic abnormalities have been reported in these individuals. How these metabolic abnormalities are exacerbated by aging is also not known.MethodsB cells were isolated by magnetic sorting from the blood of young and elderly HIV + individuals, as well as from the blood of age-matched healthy controls. We evaluated the composition of the B cell pool by flow cytometry, the expression of RNA for pro-inflammatory and metabolic markers by qPCR and their metabolic status using a Seahorse XFp extracellular flux analyzer.ResultsIn this study we have evaluated for the first time the metabolic phenotype of B cells from young and elderly HIV + individuals as compared to those obtained from age-matched healthy controls. Results show that the B cell pool of HIV + individuals is enriched in pro-inflammatory B cell subsets, expresses higher levels of RNA for pro-inflammatory markers and is hyper-metabolic, as compared to healthy controls, and more in elderly versus young HIV + individuals, suggesting that this higher metabolic phenotype of B cells is needed to support B cell IA. We have identified the subset of Double Negative (DN) B cells as the subset mainly responsible for this hyper-inflammatory and hyper-metabolic profile.ConclusionsOur results identify a relationship between intrinsic B cell inflammation and metabolism in HIV + individuals and suggest that metabolic pathways in B cells from HIV + individuals may be targeted to reduce inflammaging and IA and improve B cell function and antibody responses.
Highlights
HIV infection induces inflammaging and chronic immune activation (IA), which are negatively associated with protective humoral immunity
In this study we have evaluated the metabolic profile of B cells isolated from the blood of young and elderly HIV infected (HIV+) individuals, as compared to those isolated from the blood of age-matched healthy controls
Our results suggest the intriguing possibility that metabolic pathways in B cells from HIV + individuals may be targeted to limit inflammaging and IA and improve B cell function and antibody responses in this vulnerable population
Summary
HIV infection induces inflammaging and chronic immune activation (IA), which are negatively associated with protective humoral immunity. The metabolic requirements of B cell responses in HIV infected (HIV+) individuals are not known, metabolic abnormalities have been reported in these individuals How these metabolic abnormalities are exacerbated by aging is not known. HIV infection induces low-grade systemic inflammation, inflammaging [1] and chronic immune activation (IA), which are negatively associated with immune responses through functional impairment of B cells, T cells, monocytes, NK and dendritic cells. In HIV + individuals, metabolic abnormalities have been reported and associated with the effects of the drugs themselves as well as with the irreversible damage of metabolic tissues that started before the initiation of the treatment [6] How these metabolic abnormalities are exacerbated by aging is not fully understood. It has been hypothesized that the age-associated changes in metabolism [7], increased metabolic stress [7, 8] and reduced clearance of metabolic waste [9] may represent an additional source of inflammatory stimuli driving inflammaging and IA
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