Effects On The Biological Characteristics Of Trichinella Spiralis In Different Stage Of Life Cycle In Mice Treated With TLRs Agonists

Trichinosis is a food-borne zoonotic disease that has a significant hazard to human and animal health,society and economy,and is caused by live in mammalian striated muscle cells of host.Trichinosis has a widespread distribution in China or the worldwide,bring serious economic losses to the animal breeding industry and hazard to public health.During the long-term evolution of trichinella spiralis,it keep survival by inhibiting immune response and escape the host immune rejection.The parasitic biological character make it successfully invasive and alive.The ability of trichinella spiralis had enhanced theinfection risk in hosts Immune escape has become an insurmountable bottleneck in the development of effective immunoprotective agents(vaccines).Toll-like receptors(TLRs)play an important role in signaling pathways of numerous host immune defense systems.Development of TLRs agonists are making good progress as potential anti-trichomonas immune escape agents.The expression levels of TLRs in different stages of Trichinella spiralis infection were detected by real-time fluorescence quantitative PCR.The expression levels of interleukin-2(IL-2)interleukin-10(IL-4),interleukin-10(IL-10)and interferon-u(INF-?)were detected by ELISA.The results showed that Trichinella spiralis and its products could regulate the immune response of the host in different degrees.The regulation feature included the TH1 and TH2 reaction was dominant in the larval and the newborn larvae stage respectively.At the beginning of infection,TLR1,TLR3,TLR4,TLR7 and TLR9 were up-regulated.Almost all TLRs were down-regulated in the newborn larval stage,which indicated that neonatal larvae could inhibit most TLRs expression and signal transduction.A wide range of inhibitory trichinosis can regulate the expression of TLRs and their signaling pathways to the host immune response.The expression of TLRs in different stages of Trichinella spiralis infection also change the regulation of TLR signal transduction pathways.It indicating that Toll-like receptors play an important role during Trichinella infection.As results of Toll-like receptor expression level change during Trichinella infection,trichinella infection can regulate Th1,Th2 response to induce T lymphocytes and cytokine production and to alter the function of antigen-presenting cells.Based on the above studies,The experimental mice infected with trichinella spiralis were given the reported TLRs agonists poly(I:C),LPS-EB Biotin,TL8-506 and OND M362 in the tail vein to detect the expression level of TLRs.The mice were sacrificed at 0,3,6,9,12,15,18,21,28 and 35 days after infection.The larvae were collected and counted by artificial gastric juice digestion.To investigate the TLR expression level in the Trichinella spiralis infection mice treated with four TLRs agonists,Th1/Th2 cytokines production level of blood was analyzed.The results showed that TLRs agonists could activate TLRs and significant increased Th1-related cytokines IL-2 and IFN-? levels in the infected mice treated with TLRs agonists.Conversely,Th2-related cytokines IL-4 and IL-10 were decreased.The number of Trichinella spiralis was counted in 35 days after infection.The number of muscle larvae decreased after TLRs agonists treatment.The study provide evidence that the TLR3 agonists(I: C),LPS-EB,Biotin and TL8-506 OND M362 were able to interfere with Trichinella spiralis infection.The treatment effect of the poly(I: C)of TLR3 agonist was the best in all candidate agonists.In this study,we had evaluated the interference effect of four TLRs agonists on Trichinella spiralis infection and gotten the best TLRs agonists that could prevent the escape of Trichinella spiralis by test.This study will benefit to the development of vaccines against human and animal trichinellosis,but also reference to the development of other parasitic vaccines.