IL-9 Deficiency Promotes Pulmonary Th17 Response in Murine Model of Pneumocystis Infection

Abstract

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IntroductionPneumocystis 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 methodsMice 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.ResultsReduced 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.ConclusionAlthough 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.

Keywords

• Pneumocystis pneumonia
• IL-9
• Th17 cells
• IL-23
• alveolar macrophages