Aureobasidium pullulans-cultured fluid induces IL-18 production, leading to Th1-polarization during influenza A virus infection
Aureobasidium pullulans-cultured fluid induces IL-18 production, leading to Th1-polarization during influenza A virus infection
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DOI：
10.1093/jb/mvx062
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发表时间：
2018-01-01
影响因子：
2.7
通讯作者：
Oshiumi, Hiroyuki
中科院分区：
文献类型：
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作者：
Fujikura, Daisuke;Muramatsu, Daisuke;Oshiumi, Hiroyuki
具有病原体相关分子模式的几种微生物分子刺激宿主先天免疫应答。先天性免疫系统通过细胞因子产生和抗原呈递在激活获得性免疫应答中起关键作用。先前的研究表明，含有β-葡聚糖的出芽短梗霉培养液（AP-CF）具有佐剂活性，并使小鼠对甲型流感病毒感染具有抵抗力;然而，其潜在机制仍然难以捉摸。在这项研究中，我们研究了对AP-CF的天然免疫应答。我们发现，腹腔注射AP-CF在甲型流感病毒感染期间增加了血清IL-18水平和脾脏产生IFN-γ的CD 4（+）细胞数量。AP-CF的佐剂作用与明矾的佐剂作用不同，已知明矾具有刺激Th 2免疫应答的能力。此外，AP-CF注射几乎没有增加腹膜嗜中性粒细胞和炎性巨噬细胞的数量，而明矾注射显著增加嗜中性粒细胞和炎性巨噬细胞的数量，表明与明矾相比，AP-CF是弱的炎症诱导剂。AP-CF诱导DC 2.4细胞（一种树突状细胞系）和包括腹腔巨噬细胞在内的腹腔渗出液细胞产生IL-18。总的来说，我们的研究结果表明，AP-CF是一种佐剂，促进甲型流感病毒感染期间的Th 1反应。
Several microbial molecules with pathogen-associated molecular patterns stimulate host innate immune responses. The innate immune system plays a crucial role in activating acquired immune response via cytokine production and antigen presentation. Previous studies have shown that Aureobasidium pullulans-cultured fluid (AP-CF), which contains beta-glucan, exhibits adjuvant activity and renders mice resistance to influenza A virus infection; however, the underlying mechanism remains elusive. In this study, we investigated the innate immune response to AP-CF. We found that intraperitoneal administration of AP-CF increased the serum level of IL-18 and the number of splenic IFN-gamma producing CD4(+) cells during influenza A virus infection. The adjuvant effect of AP-CF was distinct from that of alum, which is known to have the ability to stimulate a Th2 immune response. In addition, AP-CF injection barely increased the number of peritoneal neutrophils and inflammatory macrophages, whereas alum injection markedly increased the number of neutrophils and inflammatory macrophages, suggesting that AP-CF is a weak inducer of inflammation compared to alum. AP-CF induced IL-18 production by DC2.4 cells, a dendritic cell line, and by peritoneal exudate cells that include peritoneal macrophages. Collectively, our findings indicate that AP-CF is an adjuvant that promotes the Th1 response during influenza A virus infection.