Data_Sheet_1_IL-9 Deficiency Promotes Pulmonary Th17 Response in Murine Model of Pneumocystis Infection.PDF

Introduction

Pneumocystis pneumonia (PCP) remains a severe complication with high mortality in immunocompromised patients. It has been well accepted that CD4⁺ T cells play a major role in controlling Pneumocystis infection. Th9 cells were the main source of IL-9 with multifaced roles depending on specific diseases. It is unclear whether IL-9/Th9 contributes to the immune response against PCP. The current study aims to explore the role of IL-9 and the effect of IL-9 on Th17 cells in murine model of PCP.

Materials and methods

Mice were intratracheally injected with 1 × 10⁶Pneumocystis organisms to establish the murine model of Pneumocystis infection. Pneumocystis burden was detected by TaqMan real-time PCR. Using IL-9-deficient (IL-9^−/−) mice, flow cytometry, real-time PCR and enzyme-linked immunosorbent assay (ELISA) were conducted to investigate the immune function related to Th17 response in defense against Pneumocystis infection.

Results

Reduced Pneumocystis burden was observed in lungs in IL-9^−/− mice compared with WT mice at 3-week postinfection. IL-9^−/−mice exhibited stronger Th17 immune responses than WT PCP mice through flow cytometer and real-time PCR. ELISA revealed higher levels of IL-17 and IL-23 in bronchoalveolar lavage fluid from IL-9^−/− mice than WT mice. And IL-9 deficiency promoted Th17 differentiation from CD4⁺ naive T cells. IL-17A neutralization increased Pneumocystis burden in IL-9^−/− mice.

Conclusion

Although similar basic clearance of Pneumocystis organisms was achieved in both WT and IL-9^−/− PCP mice, IL-9 deficiency could lower Pneumocystis organism burden and promote pulmonary Th17 cells response in the early stage of infection.