IL-17 Regulates Inflammatory Factors And INOS Expression Involved In Protective Anti-chlamydial Immunity

Objective:To investigate the role and mechanism of IL-17 during Chlamydia muridarum (Cm) infection.Methods:BALB/c mice were inoculated intranasally with 1×103 inclusion-forming units (IFUs) of Cm to induce the chlamydia pneumonitis. The mice were killed at the different days following infection. In order to determine the production of IL-17 and Th17 expansion, RT-PCR was used to detect the mRNA expression of IL-17 in the lung, and intracellular cytokine staining was used to detect the expansion of IL-17+ CD4+ T (Th17+). Anti-mouse IL-17 mAb was used to neutralize endogenous IL-17 following Cm infection. To evaluate the role of IL-17 during infection, the body weight change, the growth of organisms and histopathology in the lung were monitored and detected. A differential cell count in bronchoalveolar lavage (BAL) fluids was used to initially evaluate the changes of types of infiltrated inflammatory cells influenced by IL-17. Finally, RT-PCR was used to detect the expression of cytokine/chemokines and iNOS in the lung and the mouse pulmonary epithelial cell line (TC-1), to investigate the role mechanism of IL-17 during chlamydial infection.Results:Intranasal infection with 1×103 IFU in mice significantly induced IL-17 production in the lung and Th17 expansion in spleen cells. IL-17-neutralized mice exhibited a more severe state of disease, including greater body weight loss, higher organism growth, and much more severe pathological changes in the lung compared with IgG2a-treated mice. The percentage of neutrophils in the IL-17-neutralized mice was significantly lower than IgG2a-treated mice in BAL cells (p<0.001), and the percentages of lymphocyte and monocyte were relatively higher in the IL-17-neutralized mice than IgG2a-treated mice (p<0.01). Compared with IgG2a-treated mice, the expression of MIP-2 and IL-6 in the lung of IL-17-neutralized mice significantly decreased, however, the expression of RANTES significantly increased. IL-17 significantly increased TNF-a-induced MIP-2 and IL-6 expression in pulmonary epithelial cells but repressed RANTES expression. The expression of iNOS in the lung of IL-17-neutralized mice was significantly lower than that of IgG2a-treated mice. IL-17 potently induced IFN-γmediated iNOS expression in un-infected and Cm-infected pulmonary epithelial cells, and significantly increased IFN-γmediated intracellular Cm inhibition.Conclusion:Chlamydial lung infection can induce IL-17 production and Th17 expansion. IL-17 contributes to immune protection against chlamydial lung infection. The mechanisms include that IL-17 affects types of infiltrated inflammatory cells through regulating corresponding cytokine/chemokine expression, and IL-17 directly participates in inhibition on intracellular Cm, partially through enhancing iNOS expression and NO production in the lung of mice following chlamydial infection.