Toll-like receptor 2 contributes to liver injury by Salmonella infection through Fas ligand expression on NKT cells in mice

Background & Aims: Toll-like receptors (TLRs) for bacterial constitutes are expressed not only by phagocytes but also by some subsets of T cells. We previously reported that natural killer T cells (NKT cells) play an important role in liver injury induced by Salmonella infection. In the present study, we investigated whether TLRs on NKT cells are involved in Salmonella-induced liver injury. Methods: Gene expression of TLR2 was examined in sorted natural killer, NKT, and T cells from livers of naive mice by the reverse-transcription polymerase chain reaction method. Serum alanine aminotransferase level and FasL expression on liver lymphocytes were examined in TLR2-deficient (TLR2−/−) and FasL-deficient gld/gld mice before and after intraperitoneal inoculation of Salmonella choleraesuis 31N-1 using an enzyme-linked immunosorbent assay and flow cytometry. Results: TLR2 gene was abundantly expressed by NKT cells freshly isolated from naive mice. FasL expression on liver NKT cells increased in TLR2+/− mice but not in TLR2−/− mice after Salmonella infection. Serum alanine aminotransferase level was significantly lower in the TLR2−/− and gld/gld mice than in the control mice after infection. Conclusions: TLR2 may contribute to liver injury induced by Salmonella infection via FasL induction on liver NKT cells. GASTROENTEROLOGY 2002;123:1265-1277