Helicobacter pylori Induces IL-33 Production and Recruits ST-2 to Lipid Rafts to Exacerbate Inflammation.

Kuo Kuo,Lai Lai,Huang Huang,Feng Feng,Wu Wu,Lo Lo,Liao Liao,Chen Chen

doi:10.3390/cells8101290

Abstract

Helicobacter pylori colonizes human gastric epithelial cells and contributes to the development of several gastrointestinal disorders. Interleukin (IL)-33 is involved in various immune responses, with reported proinflammatory and anti-inflammatory effects, which may be associated with colitis and colitis-associated cancer. IL-33 induces the inflammatory cascade through its receptor, suppression of tumorigenicity-2 (ST-2). Binding of IL-33 to membrane-bound ST-2 (mST-2) recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates intracellular signaling pathways. However, whether IL-33/ST-2 is triggered by H. pylori infection and whether this interaction occurs in lipid rafts remain unclear. Our study showed that both IL-33 and ST-2 expression levels were significantly elevated in H. pylori-infected cells. Confocal microscopy showed that ST-2 mobilized into the membrane lipid rafts during infection. Depletion of membrane cholesterol dampened H. pylori-induced IL-33 and IL-8 production. Furthermore, in vivo studies revealed IL-33/ST-2 upregulation, and severe leukocyte infiltration was observed in gastric tissues infected with H. pylori. Together, these results demonstrate that ST-2 recruitment into the lipid rafts serves as a platform for IL-33-dependent H. pylori infection, which aggravates inflammation in the stomach.

Highlights

Helicobacter pylori is a Gram-negative, spiral-shaped, microaerophilic bacteria that colonizes the human stomach and infects more than 50% of the human population worldwide [1]
We investigated whether H. pylori exploits lipid rafts to induce IL-33/suppression of tumorigenicity-2 (ST-2) signaling for facilitating inflammation in gastric epithelial cells
We examined whether H. pylori induces the production of processed IL-33 in gastric epithelial cells using three human stomach-derived cell lines: AGS, SCM-1, and TSGH-9201

Summary

Introduction

Helicobacter pylori is a Gram-negative, spiral-shaped, microaerophilic bacteria that colonizes the human stomach and infects more than 50% of the human population worldwide [1]. Patients infected with H. pylori typically present with gastrointestinal-associated disorders, such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma [2]. H. pylori induces gastric inflammation through the activation of the nuclear factor-κB (NF-κB) signaling pathway in gastric epithelial cells, followed by the secretion of proinflammatory cytokines, such as IL-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α [3]. Recruits the IL-1 receptor accessory protein (IL-1RAcP) and subsequently activates the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in Th2 and mast cells [5]. Inflammatory proteases of microbe-infected cells cleave the full-length IL-33 into a processed form of IL-33, which effectively enhances immune cell activation and release of proinflammatory cytokines [6]

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Conclusion