IL-17 Inversely Correlated with IL-10 via the STAT3 Gene in Pneumocystis-Infected Mice.

Heng-Mo Rong,Zhao-Hui Tong,Chao Zhang,Xiao-Jun Qian,Ting Li

doi:10.1155/2019/6750861

Heng-Mo Rong, Zhao-Hui Tong + Show 3 more

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https://doi.org/10.1155/2019/6750861

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Abstract

Background Pneumocystis pneumonia (PCP) remains a common opportunistic infection in immunosuppressed individuals. Current studies showed that multiple immune cells and cytokines took part in the host defense against Pneumocystis (PC). However, the roles of IL-17 and IL-10 in the development of PCP have not been elucidated. Methods IL-10 and IL-17 levels in serum from PCP mice were detected via ELISA. The percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from IL-17–/– PCP mice and Th17 cells and IL-17+γδT cells in IL-10–/– PCP mice were examined via flow cytometry. Also, antibody neutralization examination was also performed to elucidate the relationship of IL-17 and IL-10 in the PCP model. Results We noted the increase of IL-17 and IL-10 levels in serum from mice infected with Pneumocystis. Furthermore, deficiency of IL-17 or IL-10 could lead to the delayed clearance of Pneumocystis and more severed lung damage. Our data also demonstrated that IL-17 deficiency enhanced the serum IL-10 level and the percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from PCP mice. Interestingly, we also noted an increase of the IL-17 level in serum and Th17 cell and IL-17+γδT cell percentages in the lung from IL-10–/– PCP mice. Using antibody neutralization experiments, we found that the STAT3 gene might play a critical role in the interplay of IL-17 and IL-10 in PCP. Conclusion Taken together, our results demonstrated that IL-17 and IL-10 could play the protective roles in the progression of PCP and the inverse correlation of them might be mediated by STAT3.

Highlights

Pneumocystis pneumonia (PCP) is the leading cause of lung infections in HIV-positive individuals worldwide [1, 2]
FACS data showed the significant increase of IL-10-producing B cell (5 7 ± 0 4 vs 2 9 ± 0 6%, P < 0 05, Figure 2(b)), macrophage (43 5 ± 2 5 vs 29 3 ± 1 8%, P < 0 05, Figure 2(c)), and T cell (5 8 ± 0 9 vs 2 9 ± 1 2%, P < 0 05, Figure 2(d)) percentages in the lung from Pneumocystis-infected mice than those from uninfected mice
Similar to what we found in IL-17–/– PCP mice, we noted that CD4+ T cells (10 0 ± 1 5 vs 6 5 ± 0 9%, P < 0 01, Figure 4(d)) and γδT cells (35 2 ± 2 1 vs 16 5 ± 1 6%, P < 0 01, Figure 4(e)) were expressing more IL-17 in the lung from IL-10–/

Summary

Introduction

Pneumocystis pneumonia (PCP) is the leading cause of lung infections in HIV-positive individuals worldwide [1, 2]. Recent studies have demonstrated that multiple immune cells and cytokines participate in the development of PCP. These include macrophages, Th1 cells, Th2 cells, Th17 cells, B cells, and the other immune cells. Our data demonstrated that IL-17 deficiency enhanced the serum IL-10 level and the percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from PCP mice. We noted an increase of the IL-17 level in serum and Th17 cell and IL-17+ γδT cell percentages in the lung from IL-10–/– PCP mice. Our results demonstrated that IL-17 and IL-10 could play the protective roles in the progression of PCP and the inverse correlation of them might be mediated by STAT3

Methods

Results

Conclusion