Effects Of Lipoteichoic Acid Of Bifidobacterial On NKG2 Receptor Family Of NK Cell And Fas/FasL System In B16 Tumor-Bearing Mice

Tumor immune escape is one of the most important reasons of which leading tumor can't be eliminated by body's immune system actively. Tumor can escape from immune surveillance mechanisms of host self through a number of pathways or mechanisms. Interfering tumor immune escape or enhancing function immune surveillance would conduce the body's anti-tumor effects. Bifidobacteria is one of important intestinal physiological bacterium of human and animals, and its surface molecule lipoteichoic acid (LTA) has been proven to have anti-tumor effects, but the role of LTA in reversal tumor immune escape has not been reported. NKG2 receptor family of NK cell and the Fas/FasL system are the major pathways in mechanism of tumor immune escape. In the study, we established melanoma animal model with B16 cells and observed the changes of NKG2 family of receptors and Fas/FasL system by BLTA treatment, studied the effects of BLTA on immune cell killing activity and tumor immune escape of tumor-bearing mice and explored the anti-tumor mechanisms of bifidobacterium Lipoteichoic acid (BLTA ).We want to provide the basis of experiment and theory for BLTA using in clinic to treat tumor as an immunomodulator.B16 tumor-bearing C57BL/6 mice were interfered with BLTA, killing activities of NK cell and CTL were examined by MTT assay, the protein expression of NKG2D and NKG2A of NK cell receptors in spleen cells of mice were detected by flow cytometry, the expression of the tumor-infiltrating CD4+ and CD8+ lymphocytes in tumor tissue were detected by immunohistochemistry, the changes of Rae-1, H60, Qa -1b mRNA which were corresponding ligands of NKG2 receptor family in tumor tissue and the expression of Fas and FasL mRNA in tumor tissue and spleen were detected by RT-PCR, the protein expression of Fas, FasL in tumor tissue and lymphocytes of spleen were detected by immunohistochemistry and western blot.The results showed that BLTA can promote the killing activity of NK cell and CTL cell in dose-dependent manner. The expression of NKG2D receptor on NK cells in B16 tumor-bearing mice were significantly increased after treatment with BLTA (P<0.05), the expression of NKG2A of NK cells decreased slightly (P>0.05). At the same time,both the mRNA expression of Rae-1 and H60 which are the ligands of NKG2D were enhanced in tumor tissue after treatment with BLTA in B16 tumor-bearing mice (P < 0.05), the mRNA expression of Qa-1b that is corresponding ligand of NKG2A was down regulated (P<0.05). Compared with NS control group, CD8 + lymphocyte infiltrated largely in the tumor tissue after treatment with BLTA in B16 tumor-bearing mice. The mRNA and protein expression of Fas, FasL in the tumor tissue were significantly up regulated (P<0.05) and the mRNA and protein expression of Fas, FasL in the spleen tissue were down regulated (P<0.05).The results above indicated that BLTA can enhance the cell killing activity of NK cell and CTL by regulating the NK cell receptor and Fas/FasL system, to promote apoptosis of tumor cells, and reverse the phenomenon of tumor immune escape in tumor-bearing mice, thereby enhancing anti-tumor effect further.