Role of Interleukin-33 in Staphylococcus epidermidis-Induced Septicemia

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.

A Novel Bifunctional Fusion Protein (Anti-IL-17A-sST2) Protects against Acute Liver Failure, Modulating the TLR4/MyD88 Pathway and NLRP3 Inflammasome Activation

“…Emerging evidence showed that sST2 injection inhibited LPS-induced IL-6 and NF-κB pathways, regulated the immune response of macrophages, followed by a reduced production of inflammatory factors, and decreased LPS-mediated mortality [26][27][28][29]. Furthermore, the study showed that the IL-33/ST2 axis played a critical role in regulating the homeostasis of Th17 cells, with sST2 administration leading to increased serum levels of IL-17A [30][31][32]. Therefore, whether sST2 treatment can ameliorate LPS/D-GalN-induced acute liver injury still requires further investigation.…”

Antibacterial Mechanism of Patrinia scabiosaefolia Against Methicillin Resistant Staphylococcus epidermidis

“…1 With the widespread use of indwelling medical devices and implanted foreign bodies, S. epidermidis has become a significant threat to medical device associated infections (MDAI), including catheter-related bloodstream and surgical site infections, infective endocarditis, and so on. [2][3][4][5] Recently, several studies have reported that the distribution of S. epidermidis in human clinical samples were higher than infections caused by Staphylococcus aureus in Greece and India. 6 Antibiotics have been used as the most commonly used first-line treatment for S. epidermidis.…”

Role of IL-33-ST2 pathway in regulating inflammation: current evidence and future perspectives

“…Moreover, sST2 levels may be correlated with the severity of sepsis, and the early identification of the cause of septic shock in patients [ 53 ]. These data suggest that ST2 treatment inhibits the mobilization of inflammatory monocytes in Staphylococcus epidermidis-induced sepsis [ 54 ]. Notably, high levels of IL-33 significantly aggravated tissue damage in the lungs, liver, and kidneys of mice.…”