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

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.

Signatures of B Cell Receptor Repertoire Following Pneumocystis Infection

“…In addition to IGHV1-26, which remained the most frequently used IGHV gene segment in each sample, the usage frequency of IGHV9-3 elevated after Pneumocystis infection, and it became the second most frequently used IGHV gene segment in the 2 and 3 w samples. In terms of the previous research of our group, the fungal burden of Pneumocystis peaked 3 weeks post-infection and then gradually cleared (Li et al, 2018;Rong et al, 2019b;. The increased usage of IGHV9-3 might provide a direction for further study of finding prognostic or diagnostic biomarkers for Pneumocystis pneumonia.…”

Immune Response in Pneumocystis Infections According to the Host Immune System Status

“…Pro-inflammatory Th17 response is also stimulated by Pneumocystis sp. infection [ 16 , 33 ]. The anti-inflammatory balance is provided by Tregs and the cytokine IL-10 which also increase in the infected lungs of immunocompetent mice [ 30 , 33 ].…”

“…However, rodent studies show that specific depletion of IL-10 or Tregs leads to a faster clearance of the fungus with a higher inflammation [ 30 , 63 , 64 ]. Only Rong et al find a delayed clearance in the absence of IL-10 [ 33 ].…”

“…infection [16,33]. The anti-inflammatory balance is provided by Tregs and the cytokine IL-10 which also increase in the infected lungs of immunocompetent mice [30,33]. Some studies have observed that the stage of Pneumocystis sp.…”

Pneumocystis Pneumonia: Checkpoint Inhibition to the Rescue?

“…Also, the significance of an increase in Th1 and Th17 cells 3 to 4 weeks after infection in PD-1 2/2 animals is unclear. Previous work demonstrated no role for IL-17 in pathogen clearance in PCP in mice (11), although contradictory data exist (13). Thus, a mechanistic function of these CD4 1 subsets in the context of PD-1 inhibition remains to be elucidated.…”