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

First Author  Andris F Year  2011
Journal  J Immunol Volume  186
Issue  4 Pages  2245-53
PubMed ID  21248260 Mgi Jnum  J:169140
Mgi Id  MGI:4939941 Doi  10.4049/jimmunol.1002333
Citation  Andris F, et al. (2011) Metabolic stress boosts humoral responses in vivo independently of inflammasome and inflammatory reaction. J Immunol 186(4):2245-53
abstractText  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-beta-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.
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