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

Publication Type:

Journal Article

Source:

Journal of immunology (Baltimore, Md. : 1950), Volume 186, Issue 4, p.2245-53 (2011)

Keywords:

Adenosine Triphosphate, Adjuvants, Immunologic, Aminoimidazole Carboxamide, Animals, Carrier Proteins, Cells, Cultured, Immunoglobulin G, Inflammasomes, INFLAMMATION, MICE, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Oligomycins, Ribonucleotides, Stress, Physiological, Up-Regulation

Abstract:

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-╬▓-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.