The Mechanism Of The Role Of Caspase-1 In Streptococcus Equi Subsp.zooepidemicus Infection

Streptococcus equi ssp.zooepidemicus(S.zooepidemicus,SEZ)is a Lancefield group C streptococcus,generally associated with opportunistic infection of a wide range of animals.It mostly and notably infected with pig in china,which led to significant welfare and economic costs.The inflammasome are innate immune system receptors and sensors that regulate the activation of caspase-1,which promote the maturation and secretion of proinflammatory cytokines IL-1? and IL-18.In the process of continuous evolution,pathogens have developed multiple strategies to avoid recognition of the immune system and regulates programmed cell death and thus enhance their ability to induce disease.Inflammasome is associated with the occurrence and development of various diseases caused by microbial infection,and the identification of molecules signaling pathway may provide new drug targets for the SEZ infection.In this study,we characterization of the caspase-1 and IL-1? expression in vivo and vitro.Results show that the m RNA transcription level of IL-1?,IL-6,IL-18,TNF-? and NLRP3 signal pathway related molecules in RAW264.7 were significant increased after SEZ challenge;The caspase-1 activation,IL-1? maturation and secretion in macrophage were induced by SEZ infection.Furthermore,we found that the secretion of IL-1? was significant decreased after the inhibitor Ac-YVAD-cmk treatment;To assess the effect of caspase-1 on IL-1? maturation,mice peritoneal macrophage were infected with SEZ.The result indicated that the maturation and secretion of IL-1? depends on the activation of caspase-1.We identified that m RNA transcription level of caspase-1 and IL-1? in WT mice spleen were significant enhanced,also the protein level of cleave-IL-1? significantly higher than KO mice.To examine the capacity of bacterial clearance,WT and KO mice were intraperitoneal injection with SEZ.The results show that bacterial loads in peritoneal fluid,spleen,liver,kidney and lung significantly increased in KO mice compere with WT mice,suggested that the absence of caspase-1 can promote the proliferation and diffusion of SEZ in mice;The survival of WT and KO mice after challenge with SEZ,results indicated that caspase-1 deficiency accelerated the death of KO mice.Collectively,our data suggest that caspase-1 play an important role in preventing S.zooepidemicus challenge.