Abstract
BackgroundTrichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways.Methods and findingsAfter blocking with anti-TLR2 and TLR4 antibodies, the binding of Ts-Hsp70 to DCs was significantly reduced. The reduced binding effects were also found in TLR2 and TLR4 knockout (TLR2-/- and TLR4-/-) DCs. The expression of TLR2 and TLR4 on DCs was upregulated after treatment with Ts-Hsp70 in vitro. These results suggest that Ts-Hsp70 is able to directly bind to TLR2 and TLR4 on the surface of mouse bone morrow-derived DCs. In addition, the expression of the co-stimulatory molecules (CD80, CD83) on Ts-Hsp70-induced DCs was reduced in TLR2-/- and TLR4-/- mice. More evidence showed that Ts-Hsp70 reduced its activation on TLR2/4 knockout DCs to subsequently activate the naïve T-cells. Furthermore, Ts-Hsp70 elicited protective immunity against T. spiralis infection was reduced in TLR2-/- and TLR4-/- mice correlating with the reduced humoral and cellular immune responses.ConclusionThis study demonstrates that Ts-Hsp70 activates DCs through TLR2 and TLR4, and TLR2 and TLR4 play important roles in Ts-Hsp70-induced DCs activation and immune responses.
Highlights
Trichinellosis is a serious food-borne parasitic zoonosis caused by eating raw or undercooked meats contaminated with larvae of Trichinella spiralis [1, 2]
This study demonstrates that Ts-Hsp70 activates dendritic cells (DCs) through TLR2 and TLR4, and TLR2 and TLR4 play important roles in Ts-Hsp70-induced DCs activation and immune responses
We investigated whether rTs-Hsp70 activated DCs via TLR2 or TLR4, and what role the TLR2 and TLR4 played in the protective immunity induced by immunization with rTs-Hsp70 against T. spiralis infection
Summary
Trichinellosis is a serious food-borne parasitic zoonosis caused by eating raw or undercooked meats contaminated with larvae of Trichinella spiralis [1, 2]. Many studies have showed that Hsps from parasites [11, 12] or bacteria [13] exhibited potent immunogenicity and induced protective immunity against specific infections, these proteins have become momentous target proteins in vaccine development against various infections. Ts-Hsp has been proved to be a good vaccine candidate against T. spiralis infection, mice immunized with E. coli expressed recombinant Ts-Hsp (rTs-Hsp70) formulated with Freund’s adjuvant produced 37% muscle larvae reduction compared with control mice [14]. The rTsHsp70-stimulated DCs enabled to activate CD4+ T cell and prime a protective immunity in mice against T. spiralis infection [15]. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp through TLR2 and/or TLR4 pathways.
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