| Objective:IL-17, which is a cytokine mainly secreted by CD4+ cells, plays a pivotal role in host anti-infection, anti-tumor and autoimmune diseases, and is a bridge between innate and adaptive immune response. The immune protective role of IL-17 in host against intracellular bacterial infection was firstly investigated by using a mouse model of chlamydia airway infection in this study. Innate immune response is the first line of defense against infection. Further, the effect of IL-17 on proliferation, activation and function of PMN, NK and ??T innate cells were discussed. The research results will add new contents on the mechanism of IL-17 on host against chlamydia immune protection. Methods:WT mice and IL-17-/- mice were inoculated intranasally with 1×103 inclusion-forming units(IFU) of Chlamydia muridarum(Cm) to induce the mouse Chlamydia pneumonitis. To investigate the protective role of IL-17 during Cm infection, the body weight change, growth of organisms and histopathology in the lung were monitored at different time points post infection. Percent and absolute number of CD11b+Gr-1+ PMN, CD3-NK1.1+ NK and CD3+TCR??+T ??T cells were determined by flow cytometry to evaluate the effects of IL-17 on the proliferate of innate immune cells. To study the effects of IL-17 on activation of NK cells, the cells were stained with anti mouse CD69 antibody and CD69 express were detected by flow cytometry. IFN? producion of NK and ??T cells in the lung and spleen in WT and IL-17-/- mice were detected by intracellular staining to investigate the effects of IL-17 on cytokines production of NK and ??T cells. IL-6, MIP-2 and KC mRNA expression in lung were measured by using RT-PCR to evaluate whether IL-17 promotes the recruitment of PMN by inducing expression of chemokines or not. Results:Chlamydial pneumonia was induced in mice by intranasal inoculation of Cm. The body weight of WT mice and IL-17-/- mice decreased at day3 post infection and the body weight of IL-17-/- mice continuous declination compared with WT mice, which body weight started to rise from day 7 post infection. IL-17-/- mice had much higher chlamydia growth and more severe pathological changes in the lung on day 7 and day 14 post infection compared with WT mice which indicates that IL-17 plays a protective role in Cm airway infection. Next, the mechanism of IL-17 against chlamydia immune protection, especially the effects of IL-17 on innate immune cells, include PMN, NK and ??T was investigated.(1) PMN: percent and absolute number of PMN in BAL, lung and spleen from IL-17-/- mice were significantly lower than WT mice at day3 and day7(P<0.001,P<0.01, P<0.05) following Cm infection. The mRNA expression of IL-6, MIP-2 and KC in the lung of IL-17-/- mice significantly decreased(P<0.05,P<0.001,P<0.001) on day 7 post infecion, which were consistent with the proliferation of PMN. These results indicate that IL-17 may promote the PMN recruitment by inducing PMN chemokines production.(2)NK cells: the proliferation, activation molecule CD69 expression and IFN? production of NK cells were significantly decreased on IL-17-/- mice than WT mice, which indicated that IL-17 plays an important role on proliferation, activation and cytokines production of NK cells during chlamydia infection.(3)??T cells: there is no significant difference on CD3+TCR??+T proliferation and IFN? production in the lung and spleen between IL-17-/- mice and WT mice at 3 and 7 days post infection following Cm infection. Conclusions:Chlamydial pneumonitis was induced in mice following Cm airway infection. IL-17 plays a protective role during Cm lung infection by regulating the host against chlamydia innate immune response. IL-17 promoted the recruitment of PMN to the lung by inducing chemokines, such as IL-6, MIP-2 and KC expression. Furthermore, IL-17 promoted the proliferation, activation and cytokines production of NK cells in the lung during chlamydia infection. There is no effects of IL-17 on proliferation and IFN? production of ??T cells during chlamydial lung inflammation. |
PDF Full Text Request