读“Inhibition of TLR signaling by

注：读文献后感，麻烦有心人帮忙修改一下语法之类的。

Translocatedintimin receptor (Tir) protein is one of the pathogenic agents for enteropathogenic Escherichia coli. The researcher found that the Tir protein not only plays important role in pedestal formation, but also containing two immunoreceptor tyrosine-based inhibition motifs (ITIMs). However, the function of ITIMs regions in the Tir protein is not clear, especially the function in the regulation of host immune response. ITIM motif is used in host cells to negatively regulate the immune response.The researchers found that the Tir protein can interact with SHP-1 like the ITIM in host cells. Only when the tyrosine residual phosphorylated in ITIM regions, Tir protein can interact with the SHP-1 protein. In addition, the Tir protein will enhance the SHP-1 binding to TRAF6 molecule, which is a critical mediator of the TLR2-TLR4-MyD88 signaling pathway. When SHP-1 bound to TRAF6, the level of ubiquitination for TRAF6 will decrease, which leads to the block of the downstream events. Also the phosphorylation of the tyrosine residual in ITIM regions of Tir protein inhibits cytokine production through SHP-1 pathway. From all these experiments results, the authors derive the conclusion that the ITIM containing protein Tir can inhibit the host innate immune response. And this is a previously unknown mechanism for pathogen subverting host immune response.