[ODP-169] サルモネラ線毛タンパクはTLRを介してIFN-βの発現を誘導する
Type 1 fimbriae are proteinaceous filamentous structures that are present on the surface of many members of the Enterobacteriaceae. They are mainly composed of major subunit protein FimA and adhesive protein FimH. Here, we investigated the involvement of type 1 fimbriae in the induction of interferon-β (IFN-β) expression in macrophages infected with Salmonella enterica serovar Typhimurium.
The level of IFN-β expression was lower in macrophages infected with fimA or fimH mutant Salmonella than in those infected with wild-type Salmonella. Treatment of macrophages with purified recombinant FimH protein, but not FimA, resulted in the activation of the mitogen-activated protein kinases and nuclear factor kappa B signaling pathways, leading to the expression of not only IFN-β but also pro-inflammatory cytokines, such as IL-6 and tumor necrosis factor alpha. The expression of FimH-induced IFN-β was inhibited by treatment with the Toll-like receptor 4 (TLR4) inhibitor TAK-242 and an anti-TLR2 antibody. Furthermore, FimH treatment stimulated HEK293 cells expressing TLR4 in the presence of MD-2 and CD14 or TLR2. Collectively, FimH is recognized by not only TLR4 but also TLR2 and plays a significant role in the expression of IFN-β in Salmonella-infected macrophages.