期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 2, 页码 407-417出版社
WILEY
DOI: 10.1002/eji.201444543
关键词
Adjuvants; Innate immunity; Squalene; Th1 immunity; TLR4
类别
资金
- Bill and Melinda Gates Foundation [42387]
The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) is a potent Th1-response-inducing adjuvant when formulated in a squalene oil-in-water emulsion (SE). While the innate signals triggered by TLR4 engagement are well studied, the contribution of SE remains unclear. To better understand the effect of SE on the adjuvant properties of GLA-SE, we compared the innate and adaptive immune responses elicited by immunization with different formulations: GLA without oil, SE alone or the combination, GLA-SE, in mice. Within the innate response to adjuvants, only GLA-SE displayed features of inflammasome activation, evidenced by early IL-18 secretion and IFN-gamma production in memory CD8(+) T cells and neutrophils. Such early IFN-gamma production was ablated in caspase-1/11(-/-) mice and in IL-18R1(-/-) mice. Furthermore, caspase-1/11 and IL-18 were also required for full Th1 CD4(+) T-cell induction via GLA-SE. Thus, we demonstrate that IL-18 and caspase-1/11 are components of the response to immunization with the TLR4 agonist/squalene oil-inwater based adjuvant, GLA-SE, providing implications for other adjuvants that combine oils with TLR agonists.
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