Engagement of CEACAM1 by Helicobacterpylori HopQ Is Important for the Activation of Non-Canonical NF-κB in Gastric Epithelial Cells.

Karin Taxauer,Anna Ralser,Youssef Hamway,Alisa Dietl,Michael Vieth,Karin Mink,Bernhard B Singer,Raquel Mejías-Luque,Markus Gerhard

doi:10.3390/microorganisms9081748

Abstract

The gastric pathogen Helicobacter pylori infects half of the world’s population and is a major risk factor for gastric cancer development. In order to attach to human gastric epithelial cells and inject the oncoprotein CagA into host cells, H. pylori utilizes the outer membrane protein HopQ that binds to the cell surface protein CEACAM, which can be expressed on the gastric mucosa. Once bound, H. pylori activates a number of signaling pathways, including canonical and non-canonical NF-κB. We investigated whether HopQ–CEACAM interaction is involved in activating the non-canonical NF-κB signaling pathway. Different gastric cancer cells were infected with the H. pylori wild type, or HopQ mutant strains, and the activation of non-canonical NF-κB was related to CEACAM expression levels. The correlation between CEACAM levels and the activation of non-canonical NF-κB was confirmed in human gastric tissue samples. Taken together, our findings show that the HopQ–CEACAM interaction is important for activation of the non-canonical NF-κB pathway in gastric epithelial cells.

Highlights

Helicobacter pylori colonizes the gastric mucosa of every second human being worldwide [1]
H. pylori infection occurred on a secondary loop post-canonical nuclear factor-κB (NF-κB) activation that required a functional T4SS [32]
Since HopQ is important for proper T4SS functionality, CagA translocation and NF-κB activation, we explored whether HopQ plays a role in the activation of the non-canonical NF-κB pathway

Summary

Introduction

Helicobacter pylori colonizes the gastric mucosa of every second human being worldwide [1]. The majority of infected individuals are asymptomatic, H. pylori infection can result in peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma [2,3]. MALT lymphoma arises from long-term H. pylori infection resulting in the growth of malignant lymphatic cell clones [4,5,6]. Early-stage gastric MALT lymphomas are antigen-dependent illnesses and H. pylori eradication therapy using antibiotics induces regression in three out of four patients [5]. Late-stage MALT lymphomas show high-grade transformation and acquire chromosomal translocations becoming antigen-independent and resistant to the eradication therapy [7]. H. pylori is one of the major risk factors for developing gastric cancer, classified as a class

Methods

Results

Discussion

Conclusion