Toll-like Receptor2is Involved In The Regulation Of Autophagy Induced By Streptococcus Suis

Streptococcus suis, an important zoonotic pathogen, is a Gram-positivepathogen that seriously harms the development of the swine industry and cause aarray of deadly infections characterized as meningitis, septicemia, arthritis,pneumonia, toxic shock-like syndrome and endocarditis. TLR2plays an importantrole in the inflammatory response caused by Streptococcus suis, which can activateTLR2and promote the expression of pro-inflammatory cytokines. Previous studieshave shown that the expression of pro-inflammatory cytokines was significantlyinhibited after the TLR2-/-mice astrocytes were stimulated by Streptococcus suis.Moreover, autophagy plays an integral role against intracellular pathogens and viral,and facilitates antigen-presenting and the clearing of intracellular pathogens.However, autophagy can also lead to programmed cell death (PCD). The currentstudies also showed that autophagy may affect the process of cancer,neurodegeneration, myopathy, growth and aging. In addition, not only Toll-likereceptors (TLRs) but also autophagy plays an important role in the innate andadapted immune, participating in the immune response against microbial infections.And it has been reported that there is interaction between TLRs and autophagy, forexample, TLRs ligands could induce autophagy, and autophagy-related proteins canalso be adjusted by TLRs signaling pathways. Therefore, we studied the relationshipbetween TLR2and Streptococcus suis type2(SS2)-induced autophagy, which mayprovide a theoretical basis for prevention and treatment of Streptococcussuis-mediated diseases and certain inflammatory disorders or autoimmune diseases.In this study, Balb/c mice were challenged by intragastric administration withSS2suspension. ELISA assay was performed to detect the expression of cytokinesecreted by the intestinal tissue cells; quantitative PCR was used to detect TLR2expression of intestinal tissue cells; and Western blot assay was carried out to detectthe expression of autophagy marker protein-LC3â…¡. The results indicated that SS2could up-regulate the expression of IL-12and IL-17A, activate TLR2and itsdownstream nuclear transcription factor NF-kappaB, and induce autophagy of the intestinal tissue cells.J774A.1macrophage cells were infected with SS2after blocking the TLR2, akind of surface receptors of host cell. The secretion of cytokine was detected byELISA; the transcriptional levels of TLR2and NF-kappaB mRNA were analysisedby quantitative PCR; and the expression of LC3â…¡was determined by Western blotassay. The results suggested that SS2can up-regulate the expression of TNF-alphaand IL-12, activate intracellular TLR2and its downstream nuclear transcriptionfactor (NF-kappaB) and induce autophagy; and blocking of the TLR2couldsignificantly inhibited the secretion of SS2-induced cytokine and autophagy.Collectively, SS2might infect mice through the digestive tract, then influencethe expression of cytokines, TLR2and autophagy, which provided the theoreticalbasis for development of animal model of Streptococcus suis-mediated infections;TLR2was involved in the regulation of SS2-induced autophagy, which mayrepresent a new target for prevention and treatment of certain autoimmune diseases,cancer, aging or other diseases.