[The regulatory effect of dendritic cells on Th17 cell differentiation and function in mouse infected with Plasmodium yoelii].
摘要
Objective: To investigate the regulatory effect of dendritic cells (DCs) on Th17 cell differentiation and function during mouse infection with Plasmodium yoelii 17XL strain (Py17XL) and the underlying mechanisms. Methods: Twelve female BALB/c mice were randomly assigned into the infection group (Py17XL), the TLR4 blocking group (Py17XL + TLR4), TLR9 blocking group (Py17XL + TLR9), and TLR4 and TLR9 combined blocking group (Py17XL + TLR4+TLR9)(n=3 in each group). Mice in the Py17XL + TLR4 or the Py17XL + TLR9 group received intraperitoneal injection of 10 μg anti-TLR4 or 50 μg anti-TLR9 antibody (both 0.4 ml) to block DCs function at one day before infection. The Py17XL group received same volume of PBS. All groups were then given intraperitoneal injection of 1×10(6) red blood cells (RBCs) infected with Py17XL. The RBC infection rate was calculated on days 0, 3 and 5 after infection, and spleen cell suspension was prepared, in which the CD11c+TLR9+ and Th17 cells were counted by flow cytometry. The levels of IFN-γ and IL-10 in supernatant of spleen cell culture were determined by ELISA. Results: Flow cytometry showed that DCs were successfully blocked. On day 5 after infection, 28%,29%, 31% and 16.3% mice showed parasitemia in the Py17XL group, the Py17XL + TLR4 group, the Py17XL + TLR9 group, and the Py17XL + TLR4 + TLR9 group, respectively, and on day 7, the proportions were 43.3%, 47.5%, 32.5% and 8%. Mice in the Py17XL group and the Py17XL + TLR4 group all died, while those in other groups began to die from day 6. There was a slow rise of parasitemia rate in the Py17XL + TLR9 group and the Py17XL + TLR4 + TLR9 group compared with the Py17XL group, with a significant extension of survival to days 11 and 15. Results of flow cytometry showed that the proportions of Th17 cells were 1.2% and 1.44% in the Py17XL + TLR9 group and the Py17XL + TLR4 + TLR9 group on day 5, both sighificantly decreased compared with the Py17XL group (1.9%)(P < 0.05, P < 0.01). ELISA reveale