Tsr Chemoreceptor Interacts With IL-8 Provoking E. coli Transmigration Across Human Lung Epithelial Cells.

Bing Han,Julie Khang,Katalin Szaszi,Yimin Li,Arthur S Slutsky,Yonghao Xu,Diana Islam,Nanshan Zhong,Haibo Zhang,Lorenzo Del Sorbo,Warren Lee,Manshu Li

doi:10.1038/srep31087

Abstract

Bacterial colonization of epithelial surfaces and subsequent transmigration across the mucosal barrier are essential for the development of infection. We hypothesized that the methyl-accepting proteins (MCPs), known as chemoreceptors expressed on Escherichia coli (E. coli) bacterial surface, play an important role in mediating bacterial transmigration. We demonstrated a direct interaction between human interleukin-8 (IL-8) and Tsr receptor, a major MCP chemoreceptor. Stimulation of human lung epithelial cell monolayer with IL-8 resulted in increased E. coli adhesion and transmigration of the native strain (RP437) and a strain expressing only Tsr (UU2373), as compared to a strain (UU2599) with Tsr truncation. The augmented E. coli adhesion and migration was associated with a higher expression of carcinoembryonic antigen-related cell adhesion molecule 6 and production of inflammatory cytokines/chemokines, and a lower expression of the tight junction protein claudin-1 and the plasma membrane protein caveolin-1 in lung epithelial cells. An increased E. coli colonization and pulmonary cytokine production induced by the RP437 and UU2373 strains was attenuated in mice challenged with the UU2599 strain. Our results suggest a critical role of the E. coli Tsr chemoreceptor in mediating bacterial colonization and transmigration across human lung epithelium during development of pulmonary infections.

Highlights

Lung infections caused by pathogens are a complex attack system, capable of interrupting the mechanical barrier functions including mucus clearance and the innate immune system
Similar results were observed when the E. coli strains were added to human lung epithelial A549 cell monolayer
We demonstrate that the E. coli Tsr chemoreceptor can directly interact with human chemokine IL-8 to facilitate E. coli adherence leading to the bacteria transmigration across human lung epithelial cells

Summary

Introduction

Lung infections caused by pathogens are a complex attack system, capable of interrupting the mechanical barrier functions including mucus clearance and the innate immune system. Infection with E. coli is initiated by bacterial colonization and adherence to the epithelial surface and subsequent transmigration across the epithelial–endothelial barrier. The MCP family, including five phenotype chemoreceptors (Tsr, Tar, Tap, Trg, and Aer) expressed on E. coli has been most extensively characterized[20]. Tsr and Tar are the most abundantly expressed chemoreceptors making approximately 10-fold more copies than the lower abundant Tap and Trg[23]. Genetic analysis has demonstrated that Tsr and Tar are uniformly conserved in motile E. coli strains, while the clade of extra-intestinal pathogenic E. coli strains underwent ancestral loss of Trg and Tap chemoreceptors[24]. We focused the present study on an investigation testing the hypothesis that Tsr has a place in mediating E. coli chemotaxis in response to stimulation with IL-8 in human lung epithelial cells

Methods

Results

Conclusion