Inter-regulation Of Th1 And Th17 Are Involved In The Protection Against Cm Lung Infection

Objective:To investigate the role of Thl and Th17 responses and the cross regulation of IFN-γand IL-17 to Th17 and Thl responses during Cm lung infection.Methods:BALB/c mice aged 6-8 weeks were inoculated intranasally with 1 X 103 IFUs of Cm to build the murine model of pneumonia. The body weight changes, mortality, pathogenesis and the growth of Cm in the lung were monitored to determine the severity of the disease. Mice were sacrificed at the different days following infection. To determine the Thl and Th17 responses in mice, RT-PCR was used to assay the mRNA expression of IFN-γ, IL-17 and their upstream cytokines IL-12 and IL-23 in the lung and intracellular cytokine staining was used to assay the proliferation of IFN-γ-CD4+T and IL-17-CD4+T cells in the spleen. Anti-mouse IFN-γand IL-17 mAbs were used to neutralize endogenous IFN-γand IL-17 following Cm lung infection. The severity of the disease was monitored to determine the role of IFN-γand IL-17 in Cm lung infection. Mice were sacrificed at day 7 post-infection. The mRNA expression of IFN-γ, IL-17 and their upstream cytokines IL-12 and IL-23 in the lung was assayed by RT-PCR, and the proliferation of IFN-γ-CD4+T and IL-17-CD4+T cells in the spleen was assayed by intracellular cytokine staining to investigate the cross regulation of IFN-γand IL-17 to Thl7 and Thl responses during Cm lung infection.Results:Intranasally infected with 1×103 IFUs of Cm in mice resulted in chlamydial mouse pneumonitis featured by body weight lost, chlamydia growth and severe pathological damage in the lung. High levels of Thl and Th17 responses were induced by Cm lung infection, including high levels of IFN-γ, IL-17 and their upstream cytokines IL-12 and IL-23 expression in the lung and IFN-γ-CD4+T and IL-17-CD4+T cells proliferation in the spleen. What's important, the IFN-γand IL-17-neutralized mice exhibited greater body weight lost, more organism growth and much more serious pathological damage. Compared with PBS control mice, the expression of IFN-γ, IL-17 and their upstream cytokines IL-12 and IL-23 in the lung and the proliferation of IFN-γ-CD4+T and IL-17-CD+T cells in the spleen significantly decreased in the IFN-γand IL-17-neutralized mice.Conclusion:Intranasally infected of Cm resulted in typical chlamydial mouse pneumonitis.Cm lung infection induced high levels of Thl and Th17 responses. IFN-γand IL-17 were both protective in Cm lung infection through cross up-regulating antigen specific Th17 and Th1 responses.