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-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / antagonists & inhibitors
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Adenosine Triphosphate / metabolism
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Adjuvants, Immunologic / pharmacology
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Carrier Proteins / metabolism
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Cells, Cultured
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Immunoglobulin G / biosynthesis*
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Inflammasomes / metabolism*
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Inflammasomes / physiology
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Inflammation / chemically induced
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Inflammation / immunology
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Inflammation / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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NLR Family, Pyrin Domain-Containing 3 Protein
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Oligomycins / pharmacology
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Ribonucleotides / pharmacology
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Stress, Physiological / immunology*
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Carrier Proteins
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Immunoglobulin G
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Inflammasomes
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nlrp3 protein, mouse
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Oligomycins
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Ribonucleotides
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Aminoimidazole Carboxamide
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Adenosine Triphosphate
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AICA ribonucleotide