A Type III Effector NleF from EHEC Inhibits Epithelial Inflammatory Cell Death by Targeting Caspase-4.

Ting Song,Jing Zhou,Hongmei Dai,Hongguang Ren,Yuan Jin,Junjie Yue,Kaiwu Li,Tingting Xu,Long Liang,Mingda Hu,Wei Zhou

doi:10.1155/2017/4101745

Abstract

Enterohemorrhagic E. coli (EHEC) is a highly pathogenic bacterial strain capable of inducing severe gastrointestinal disease. Here, we show that EHEC uses the T3SS effector NleF to counteract the host inflammatory response by dampening caspase-4-mediated inflammatory epithelial cell death and by preventing the production of IL-1β. The other two inflammatory caspases, caspase-1 and caspase-5, are not involved in EHEC ΔnleF-induced inflammatory cell death. We found that NleF not only interrupted the heterodimerization of caspase-4-p19 and caspase-4-p10, but also inhibited the interaction of caspase-1 and caspase-4. The last four amino acids of the NleF carboxy terminus are essential in inhibiting caspase-4-dependent inflammatory cell death.

Highlights

The intestinal epithelium is an essential component of the host immune defense which provides a physical barrier between the body and the outside environment [1]
The modalities of host cell death induced upon bacterial infection vary among different pathogens, host cell type, or infectious stage, the following three types of host cell death are widely used as targets for bacterial pathogens to enhance pathogenesis: apoptosis, necrosis, and pyroptosis [4]
These results clearly demonstrate that NleF helps counteract epithelial cell death responses to Enterohemorrhagic E. coli (EHEC) infection

Summary

Introduction

The intestinal epithelium is an essential component of the host immune defense which provides a physical barrier between the body and the outside environment [1]. The innate immune response represents the first active line of defense against enteric pathogens [2]. The innate immune response rapidly mediates the induction of cell death in infected host cells, the secretion of proinflammatory cytokines, and the control of invading pathogens [3]. Host cell death is a critical immune defense mechanism in response to microbial infection that sacrifices infected cells for the benefit of the remaining cells. Cell membrane rapidly ruptures and the cellular contents are released, accompanying caspase-independent inflammation [6]. Pyroptosis is known as inflammatory cell death, which is coordinated by inflammasome-mediated caspases activation and accompanied by DNA fragmentation, membrane rupture, and the release of proinflammatory cytokines, including IL-1β and IL-18. Caspase-4, and caspase-5 are critical mediators in the pyroptosis process [7]

Methods

Results

Conclusion