Regulation Of Toll-like Receptor 2 Expression And Function By Macrophages During Mycobacterium Tuberculosis Infection And Its Polymophism Association With Tuberculosis Disease.

Recent studies have implicated Toll-like receptors(TLR),especially TLR-2,as sentinel receptors that signal the interaction of macrophages with Mycobacterium tuberculosis infection.Here we report that it was much different expression and function of TLR-2 treated with BCG/PPD and the gene polymorphism association with the tuberculosis disease was based on different population.All the results indicated that TLR-2 might play an important part in the Mycobacterium tuberculosis infection,but there must be much more complicated mechanism above our knowledge.Slection 1 Regulation of Toll-like receptor 2 expression and function by macrophages treated with BCG/H37Rv-PPD.[Objictive]To study the regulation of Toll-like receptor 2 expression and function by macrophages treated with different TLR-2 agonists related with Mycobacterium tuberculosis.[Methods]Using H37Rv-PPD and BCG to stimulate U937 cell for 1h,3h,6h,12h and 24h respectively.Cells were ananlyzed by flow cytometry to detect the cell surface receptor level.Production of cytokines(TNF-α,IL-1β,IL-10) in the supernatant was tested by ELISA.Annexin V staining was performed to assay apoptosis in macrophages.[Results]The expression of Toll-like receptor 2 was up-regulated with BCG. Meanwhile,the concentration of TNF-αincreased until 3h with IL-1βincreasing and IL-10 decreasing and the percents of apoptosis cells increased gradually.The results of PPD were much different.Toll-like receptor 2 was remained high level after treated, and the peak of TNF-αconcentration delayed to 12h.IL-1βwas no obvious different and IL-10 was up-regulated.The percent of apoptosis cells were not seen increased. [Conclusion](1) Both BCG and H37Rv-PPD can active Toll-like receptor 2 signals and BCG may have more strict regulatory mechanisms to prevent the TLR-mediated response form leading to uncontrolled inflammation.(2)BCG can induce U937 cells to apoptosis which may positive correlate with Toll-like receptor 2 level and concentration of TNF-α.So we suppose that TLR-2 may participate in apopotosis in Mycobacterium tuberculosis infected macrophages.3) Altough H37Rv-PPD can activate TLR-2 signals,it can't induced macrophage apoptosis which indicated that virulence strain may have particular secreted protein to inhibit apoptosis.Selection 2 Gene polymorphisms of Toll-like receptors 2 in tuberculosis in Chinese population[Objictive]The aim of the present study was to investigate the Arg753Gln and Arg677Trp single nucleotide polymorphism of the TLR-2 gene in patients with tuberculosis among Han population in southwest China and compare the gene polymorphism distribution among different populations of various population.[Methods]A retrospective case/control study was carried out.Restriction fragment length polymorphism(PCR-RFLP) was applied to detect Arg753Gln and Arg677Trp in 77 patients and 75 healthy controls.[Results]We only found 1 patient was heterozygote in Arg753Gln(G/A) and no Arg677Trp mutation was found in both tuberculosis group and controls.[Conculusions](1) TLR-2 gene Arg753Gln and Arg677Trp can not form polymorphisms in the southwest China population.(2)TLR-2 gene Arg677Trp may not be correlated with tuberculosis susceptibility.(3) TLR-2 polymophism Arg753Gln may be engengdered by genentic heterogeneity.It may correlated with tuberculosis susceptibility in Caucasian population,and may have less value in Chinese.