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Metabolic stress boosts humoral responses in vivo independently of inflammasome and inflammatory reaction.

par Andris, Fabienne ;Denanglaire, Sébastien ;Baus, Erika ;Rongvaux, Anthony ;Steuve, Jonathan ;Flavell, R A;Leo, Oberdan
Référence The Journal of immunology, 186, 4, page (2245-2253)
Publication Publié, 2011-02-15

Article révisé par les pairs

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Résumé :

Adjuvant formulations boost humoral responses by acting through several, yet incompletely elucidated pathways. In this study, we show that oligomycin or 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR) enhances Ab production when coinjected with T cell-dependent Ags. Oligomycin and AICAR lead to intracellular ATP reduction, suggesting that metabolic stress could be sensed by immune cells and leads to increased humoral responses. AICAR promotes IL-4 and IL-21 by naive Th cells but does not affect dendritic cell activation/maturation in vitro or in vivo. Accordingly, the adjuvant effect of AICAR or oligomycin does not require MyD88 or caspase-1 expression in vivo. Because AICAR is well tolerated in humans, this compound could represent a novel and safe adjuvant promoting humoral responses in vivo with a minimal reactogenicity.