Role of Interleukin-33 in Staphylococcus epidermidis-Induced Septicemia.

Min Yang,Yiwen Wang,Qifeng Li,Jintong Tan,Yonghong Zhang,Yanjun Li

doi:10.3389/fimmu.2020.534099

Abstract

Interleukin (IL)-33 is a member of the IL-1 family, which plays an important role in inflammatory response. In this study, we evaluated the effect of IL-33 on septicemia and the underlying mechanisms by establishing a Staphylococcus epidermidis (S. epidermidis)-induced septicemic mouse model. The expression of IL-33, IL-1α, IL-1β, IL-6, IL-17A, IL-22, and PGE2 were measured by double antibody sandwich enzyme-linked immunosorbent assay, and bacterial colony formation in peripheral blood and kidneys were counted postinfection. The percentages of neutrophils, eosinophils, and inflammatory monocytes were evaluated by flow cytometry, and tissue damage was assessed by hematoxylin and eosin (H&E) staining. The survival of septicemic mice was monitored daily. IL-33 expression was significantly augmented following S. epidermidis infection. High IL-33 expression significantly decreased the survival of model mice, and aggravated the damage of lung, liver, and kidney tissues. However, administration of ST2 (receptor for IL-33) to the S. epidermidis-infected mice blocked the IL-33 signaling pathway, which elevated PGE2, IL-17A, and IL-22, and promoted healing of organ damage. In addition, ST2 suppressed the mobilization of inflammatory monocytes, but promoted the accumulation of neutrophils and eosinophils in S. epidermidis-infected mice. Inhibition of PGE2, IL-17A, and IL-22 facilitated the development of septicemia and organ damage in S. epidermidis-infected mice, as well as reducing their survival. Our findings reveal that IL-33 aggravates organ damage in septicemic mice by inhibiting PGE2, IL-17A, and IL-22 production.

Highlights

Septicemia is a systemic inflammatory response syndrome that occurs when pathogenic bacteria or conditional pathogens invade the blood circulation and multiply in the blood to produce toxins [1]
The levels of Prostaglandin E2 (PGE2), IL17A, and IL-22 were significantly decreased in the IL-33 group compared to the model group, but increased in the ST2 group (Figures 2D–F). These results suggest that IL-33 inhibits the production of PGE2, IL-17A, and IL-22 in septicemic mice
A study by Garth et al showed that the absence of IL-1RL1/ST2 signaling leads to increased production of IL-17A and IL-22, while elevated IL-33 decreased production of IL-17A and IL-22; these findings indicate that IL-33 signaling negatively regulates IL-17A and IL-22 by IL-1RL1 [33], which was similar to the results of our findings

Summary

Introduction

Septicemia is a systemic inflammatory response syndrome that occurs when pathogenic bacteria or conditional pathogens invade the blood circulation and multiply in the blood to produce toxins [1]. Similar to IL-1β and IL-18, 2 other members of the IL-1 family, IL-33 is firstly synthesized as a 31 kDa precursor, and cleaved by caspase 1 to generate mature IL-33. IL-33 has been studied in numerous inflammatory disorders, including colitis, rheumatoid arthritis, and allergic asthma, as well as sepsis [8, 9], in which IL-33/ST2 signaling contributes to organ injury and innate immunity [10, 11]

Methods

Results

Conclusion