Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Li T

PROVIDER: S-EPMC5980981 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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IL-9 Deficiency Promotes Pulmonary Th17 Response in Murine Model of <i>Pneumocystis</i> Infection.

Li Ting T Rong Heng-Mo HM Zhang Chao C Zhai Kan K Tong Zhao-Hui ZH

Frontiers in immunology 20180525

<h4>Introduction</h4><i>Pneumocystis</i> pneumonia (PCP) remains a severe complication with high mortality in immunocompromised patients. It has been well accepted that CD4<sup>+</sup> T cells play a major role in controlling <i>Pneumocystis</i> 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 ...[more]

PMID: 29887863

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Project description:In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-? signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs). In addition, in pulmonary PCM, the tolerogenic function of plasmacytoid dendritic cells was linked to the IDO1 activity. To further evaluate the function of IDO1 in pulmonary PCM, IDO1-deficient (IDO1-/-) C57BL/6 mice were intratracheally infected with P. brasiliensis yeasts and the infection analyzed at three postinfection periods regarding several parameters of disease severity and immune response. The fungal loads and tissue pathology of IDO1-/- mice were higher than their wild-type controls resulting in increased mortality rates. The evaluation of innate lymphoid cells showed an upregulated differentiation of the innate lymphoid cell 3 phenotype accompanied by a decreased expansion of ILC1 and NK cells in the lungs of infected IDO1-/- mice. DCs from these mice expressed elevated levels of costimulatory molecules and cytokine IL-6 associated with reduced production of IL-12, TNF-?, IL-1?, TGF-?, and IL-10. This response was concomitant with a marked reduction in AhR production. The absence of IDO1 expression caused an increased influx of activated Th17?cells to the lungs with a simultaneous reduction in Th1 and Treg cells. Accordingly, the suppressive cytokines IL-10, TGF-?, IL-27, and IL-35 appeared in reduced levels in the lungs of IDO1-/- mice. In conclusion, the immunological balance mediated by the axis IDO/AhR is fundamental to determine the balance between Th17/Treg cells and control the severity of pulmonary PCM.

Dataset Information

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

Publications

IL-9 Deficiency Promotes Pulmonary Th17 Response in Murine Model of <i>Pneumocystis</i> Infection.

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