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

Abstract

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 × 106 Pneumocystis 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.

Early diagnosis of psoriatic arthritis among psoriasis patients: clinical experience sharing

“…Allergic diseases are Th2-polarized diseases [36], whereas psoriasis is a Th17 disease, in general speaking, but could be a Th9-polarized disease in the gut [36,37]. This transition may explain why allergic skin disease does not coexist with PSO in our cohort, but whether the Th9 links between the Th2 [38] and Th17 [39] pathogeneses need to be further investigated. Fig.…”

“…Allergic diseases are Th2-polarized diseases [ 36 ], whereas psoriasis is a Th17 disease, in general speaking, but could be a Th9-polarized disease in the gut [ 36 , 37 ]. This transition may explain why allergic skin disease does not coexist with PSO in our cohort, but whether the Th9 links between the Th2 [ 38 ] and Th17 [ 39 ] pathogeneses need to be further investigated. Another explanation is that IL17E, also known as IL25, could propagate production of IL-4 and IL-13 in different organs, which stimulate the expansion of eosinophils [ 40 ], and link between allergic disease and psoriatic disease.…”

The Contribution of Host Cells to Pneumocystis Immunity: An Update

“…Interestingly, Th17 cells are also thought to produce IL-9 [44]; how this influences Th17 responses to Pneumocystis remains to be determined. Investigations by Li et al suggested that, despite Pneumocystis clearance in wild-type (WT) and IL-9-deficient mice, IL-9 deficiency may actually lower lung burden and promote pulmonary Th17 responses in the early stages of infection [45]. Th1 and Th2 have also been implicated in host protection against Pneumocystis .…”

Circulating and Pulmonary T-cell Populations Driving the Immune Response in Non-HIV Immunocompromised Patients with Pneumocystis jirovecii Pneumonia

“…Additionally, the IL-17/IL-23 axis was capable of extending the Th17 effector response 19, and Th17 cells are involved in the immune response during P. jirovecii infection 20. More recently, IL-9 -/- mice showed reduced P. murina burden in the lungs 21. The presence of CD8 + T cells in response to P. jirovecii infection may also be deleterious 22.…”