Metabolic stress boosts humoral responses in vivo independently of inflammasome and inflammatory reaction.
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.
Laboratoire d'Immunobiologie, Institut de Biologie et de Médecine Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium. fandris@ulb.ac.be
Fabienne
F
Andris
Sébastien
S
Denanglaire
Erika
E
Baus
Anthony
A
Rongvaux
Jonathan
J
Steuve
Richard A
RA
Flavell
Oberdan
O
Leo
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000096:biosynthesis*; D058847:Inflammasomes / Q000378:metabolism* / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009840:Oligomycins / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology; D013312:Stress, Physiological / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; D007074:Immunoglobulin G; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009840:Oligomycins; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000255:Adenosine Triphosphate; C031143:AICA ribonucleotide