Immunometabolic effects of lactate on humoral immunity in healthy individuals of different ages

Maria Romero, Kate Miller, Andrew Gelsomini, Denisse Garcia, Kevin Li, Dhananjay Suresh and Daniela Frasca ()
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Maria Romero: University of Miami Miller School of Medicine
Kate Miller: University of Miami Miller School of Medicine
Andrew Gelsomini: University of Miami Miller School of Medicine
Denisse Garcia: University of Miami Miller School of Medicine
Kevin Li: University of Miami Miller School of Medicine
Dhananjay Suresh: University of Miami Miller School of Medicine
Daniela Frasca: University of Miami Miller School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Aging is characterized by chronic systemic inflammation and metabolic changes. We compare the metabolic status of B cells from young and elderly donors and found that aging is associated with higher oxygen consumption rates, and especially higher extracellular acidification rates, measures of oxidative phosphorylation and of anaerobic glycolysis, respectively. Importantly, this higher metabolic status, which reflects age-associated expansion of pro-inflammatory B cells, is found associated with higher secretion of lactate and autoimmune antibodies after in vitro stimulation. B cells from elderly individuals induce in vitro polarization of CD4+ T cells from young individuals into pro-inflammatory CD4+ T cells through metabolic pathways mediated by lactate, which can be inhibited by targeting lactate enzymes and transporters, as well as signaling pathways supporting anaerobic glycolysis. Lactate also induces immunosenescent B cells that are glycolytic, express transcripts for multiple pro-inflammatory molecules, and are characterized by a higher metabolic status. These results altogether may have relevant clinical implications and suggest alternative targets for therapeutic interventions in the elderly and patients with inflammatory conditions and diseases.

Date: 2024
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DOI: 10.1038/s41467-024-51207-x

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