Ts-Hsp70 induces protective immunity against Trichinella spiralis infection in mouse by activating dendritic cells through TLR2 and TLR4

摘要

Author summary Trichinellosis is a serious food-borne parasitic zoonosis caused by tissue-dwelling nematode Trichinella spiralis. Vaccine development is needed as an alternative approach to control the infection in domestic livestock or in humans. Ts-Hsp70 has been identified to elicit partial protective immunity against Trichinella spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate the pathway(s) through which the Ts-Hsp70 activates DCs. Our results identified that Ts-Hsp70 could bind to DCs which was inhibited by blocking TLR2 and TLR4 with antibodies or TLR2 and TLR4 knockout. Ts-Hsp70 stimulated the expression of TLR2 and TLR4 and the co-stimulatory CD80, CD83 and CD86 on the surface of DCs which was reduced in TLR2 or TLR4 knockout mice. With TLR2 or TLR4 knockout, DCs were less stimulated by Ts-Hsp70 and subsequently reduce the activation of naïve T-cells. The protective immunity induced by Ts-Hsp70 against T. spiralis infection was also reduced in TLR2 or TLR4 knockout mice. The results conclude that Ts-Hsp70 activates DCs through activating TLR2 and TLR4 and TLR2 and TLR4 play important roles in Ts-Hsp70-induced protective immunity against Trichinella infection.