[ODP-173] Salmonella FimH is involved in the expression of pro-inflammatory cytokines in TLR4-dependent manner
Type 1 fimbriae are proteinaceous filamentous structures present on bacterial surfaces and are mainly composed of the major fimbrial protein subunit FimA and the adhesive protein FimH, which is located at the tip of the fimbrial shaft. Here, we investigated the involvement of type 1 fimbriae in the expression of pro-inflammatory cytokines in macrophages infected with Salmonella enterica serovar Typhimurium. The level of interleukin-1beta (IL-1β) mRNA was lower in macrophages infected with a fimA or fimH mutant strains 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 kinase and nuclear factor kappa B signaling pathways, leading to the expression of not only IL-1β but also of other pro-inflammatory cytokines such as IL-6 and tumor necrosis factor alpha. FimH treatment stimulated HEK293 cells expressing TLR4 and MD-2/CD14 but did not stimulate HEK293 cells expressing only TLR4. Collectively, FimH is a pathogen-associated molecular pattern of S. enterica serovar Typhimurium that is recognized by TLR4 in the presence of MD-2 and CD14 and plays a significant role in the expression of pro-inflammatory cytokines in Salmonella-infected macrophages.