Functional Study Of Mitogen-activated Protein Kinase 1 Of Toxoplasma Gondii In Host Inflammasome Pathway

Toxoplasma gondii is a kind of specific intracellular parasite, which can infect all warm hosts and lead to serious zoonosis. Innate immunity plays an important role in protecting the host against Toxoplasma gondii infection. Inflammasome is a kind of multiprotein complexes, and mainly consists of three parts: the sensor such as NLR, receptor molecule ASC and active caspase; which is another important effector after the complement of innate immune. NLRP1 and NLRP3 inflammasomes can be activated by Toxoplasma gondii infection, by regulating IL-1β and IL-18 maturation and activation to mediate inflammatory response. Mitogen activated protein kinase(MAPK) pathway, which is the major signal transduction system of Toxoplasma gondii that can regulate the growth, differentiation and proliferation of parasite, and so on. Therefore, the research which is about mitogen-activated protein kinase 1 of Toxoplasma gondii and the mechanism of inflammasome activation has important scientific significance and lays the foundation for the prevention and treatment of Toxoplasmosis.The effect of MAPK1 deletion on host inflammation level induced by Toxoplasma gondiiΔmapk1 that has been constructed and parental GT1 tachyzoites were injected into mice, so as to observe and detect the change of inflammation. The results showed that, during 4 weeks of experimental period, the mice infected GT1 had 100% mortality, compared with the GT1, mice infected Δmapk1 had 70% mortality and 30% of which were able to survive longer, suggesting that deletion of MAPK1 could significantly decrease virulence of Toxoplasma gondii in mice. Pathological sections and QRT-PCR results showed that deletion of MAPK1 could significantly reduce the pathology of liver and spleen and proliferation ability of parasite in mice. The serum cytokine data indicated that, compared with the GT1-infected group, the secretory volume of serum inflammatory cytokines IFN-γ, IL-12, TNF-α and IL-6 reduced about 50% in Δmapk1-infected group, suggesting that MAPK1 deletion of Toxoplasma gondii could significantly suppress the production of inflammatory cytokines in serum of mice. All the results showed that deletion of MAPK1 in Toxoplasma gondii could decrease the inflammation level in host.The effect of MAPK1 deletion on the activation of host inflammasome induced by Toxoplasma gondiiWestern bloting and QRT-PCR were used to analyze the degree of activation of inflammasome pathway and the translation and transcription level of factors that were related to the activation in infected mice. The results showed that, the lack of MAPK1 effected the activation level of host inflammasome pathway that induced by Toxoplasma gondii by two ways: on the one hand, by inhibiting the activation level of NLRP1 and NLRP3 inflammasomes to inhibit the shear ripening process of pro-IL-18 by caspase-1 in mice; on the other hand, by high-level IFN-β activating STAT1 transcription to induce IL-10 production and by inhibiting the expression of STAT3 to reduce pro-IL-18 production, thereby inhibiting IL-18 mature and reducing the host inflammation level induced by Toxoplasma gondii.