Sun Xiao, Hosomi Koji, Shimoyama Atsushi, Yoshii Ken, Lan Huangwenxian, Wang Yunru, Yamaura Haruki, Nagatake Takahiro, Ishii Ken J, Akira Shizuo, Kiyono Hiroshi, Fukase Koichi, Kunisawa Jun
Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, Collaborative Research Center for Health and Medicine, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, Japan.
Int Immunopharmacol. 2023 Apr;117:109852. doi: 10.1016/j.intimp.2023.109852. Epub 2023 Feb 18.
Alcaligenes faecalis was previously identified as an intestinal lymphoid tissue-resident commensal bacteria, and our subsequent studies showed that lipopolysaccharide and its core active element (i.e., lipid A) have a potent adjuvant activity to promote preferentially antigen-specific Th17 response and antibody production. Here, we compared A. faecalis lipid A (ALA) with monophosphoryl lipid A, a licensed lipid A-based adjuvant, to elucidate the immunological mechanism underlying the adjuvant properties of ALA. Compared with monophosphoryl lipid A, ALA induced higher levels of MHC class II molecules and costimulatory CD40, CD80, and CD86 on dendritic cells (DCs), which in turn resulted in strong T cell activation. Moreover, ALA more effectively promoted the production of IL-6 and IL-23 from DCs than did monophosphoryl lipid A, thus leading to preferential induction of Th17 and Th1 cells. As underlying mechanisms, we found that the ALA-TLR4 axis stimulated both MyD88- and TRIF-mediated signaling pathways, whereas monophosphoryl lipid A was biased toward TRIF signaling. These findings revealed the effects of ALA on DCs and T cells and its induction pattern on signaling pathways.
粪产碱杆菌先前被鉴定为一种驻留在肠道淋巴组织中的共生细菌，我们随后的研究表明，脂多糖及其核心活性成分（即脂质A）具有强大的佐剂活性，可优先促进抗原特异性Th17反应和抗体产生。在此，我们将粪产碱杆菌脂质A（ALA）与单磷酰脂质A（一种已获许可的基于脂质A的佐剂）进行比较，以阐明ALA佐剂特性背后的免疫机制。与单磷酰脂质A相比，ALA在树突状细胞（DC）上诱导出更高水平的MHC II类分子以及共刺激分子CD40、CD80和CD86，进而导致强烈的T细胞活化。此外，与单磷酰脂质A相比，ALA能更有效地促进DC产生IL-6和IL-23，从而优先诱导Th17和Th1细胞。作为潜在机制，我们发现ALA-TLR4轴刺激了MyD88和TRIF介导的信号通路，而单磷酰脂质A则偏向于TRIF信号通路。这些发现揭示了ALA对DC和T细胞的作用及其对信号通路的诱导模式。
