Toll- like receptor 2 drives Th17 cell activation in inflammatory response to hepatitis B virus infection

Objective To investigate the relationship between Toll- like receptor 2 ( TLR2) in peripheral blood mononuclear cells ( PBMCs) and T helper 17 ( Th17) cells among hepatitis B patients and to provide a theoretical and experimental basis for the study on the mechanism of inflammatory response to hepatitis B virus ( HBV) infection. Methods Thirty- four previously untreated patients with hepatitis B ( 24 cases of chronic hepatitis B and 10 cases of acute hepatitis B) who visited or were hospitalized in the Center of Infectious Diseases, Tangdu Hospital, from July 2012 to July 2013, as well as ten healthy controls, were enrolled in this study. PBMCs were isolated and stimulated by HBV ( genotype C) envelope peptides ( specific) or propylene glycol monomethyl ether acetate ( PMA) plus ionomycin ( nonspecific) . Flow cytometry was performed to measure the expression of TLR2 and the percentage of Th17 cells. PBMCs were further stimulated by TLR2 agonist Pam3Csk4, and the changes in percentage of Th17 cells were evaluated. Comparison between groups was made by Kruskal-Wallis H test. Results When stimulated by PMA plus ionomycin, patients with chronic hepatitis B had a significantly higher percentage of Th17 cells than patients with acute hepatitis B and healthy controls [ ( 4. 08 ± 1. 78) % vs ( 1. 85 ± 1. 28) %, P = 0. 0009; ( 4. 08 ±1. 78) % vs ( 2. 09 ± 0. 53) %, P = 0. 0004], while the percentages of TLR2+and IL- 17A+TLR2+T cells in peripheral blood CD3+CD4+T cells showed no significant differences between patients with acute hepatitis B, patients with chronic hepatitis B, and healthy controls ( P > 0. 05 for all) . When stimulated by HBV envelope peptides, patients with chronic hepatitis B had significantly higher percentages of IL- 17A+T cells and TLR2+T cells than patients with acute hepatitis B [ ( 5. 45 ± 1. 61) % vs ( 3. 20 ± 1. 13) %, P = 0. 0006; ( 5. 19± 3. 18) % vs ( 1. 88 ± 1. 30) %, P = 0. 0006]. After the addition of Pam3Csk4, patients with chronic hepatitis B had a significantly increased percentage of Th17 cells, while patients with acute hepatitis B had a nonsignificantly increased percentage of Th17 cells. Conclusion TLR2 could directly influence Th17 cell responses, thereby playing a proinflammatory role in the immune response to HBV infection.