JMM Editor’s Choice: How does Helicobacter pylori cause inflammation?

Posted on April 3, 2020   by Microbiology Society

The Journal of Medical Microbiology (JMM) is a journal published by the Microbiology Society, focused on providing comprehensive coverage of medical, dental and veterinary microbiology and infectious diseases, including bacteriology, virology, mycology and parasitology. This month, Professor Arunaloke Chakrabarti discusses the paper ‘N-terminal region of Helicobacter pylori CagA induces IL-8 production in gastric epithelial cells via the β1 integrin receptor’, which was selected as Editor’s Choice from the March issue of JMM.

“Multiple epidemiological studies have shown a strong association of Helicobacter pylori with gastric cancer. However, the pathogenesis of gastric cancer induced by H. pylori cytotoxin-associated antigen (CagA) is not currently understood, though it remains of interest to many scientists in this field. From whole genome sequencing, interleukin-8 (IL-8) was found to be the single most upregulated gene in H. pylori exposed to gastric epithelium.

Previously, many researchers have focused on the role of the C-terminal domain of cytotoxin-associated antigen A (CagA) in IL-8 production. However, the authors in the present study evaluated the N-terminal region of CagA and focused on 303-456 residues, as they interact with integrin b1 (ITGB1). They showed that 303-456 residues of the N-terminal portion of extracellular CagA can induce IL-8 production by activating p38 through ITGB1 or MAPK ERK1/2 signal pathway. Though the authors acknowledge the present result is still not sufficient for the evidence of extracellular CagA-induced IL8 secretion, this is an important step in understanding pathogenesis of gastric cancer.”

N-terminal region of Helicobacter pylori CagA induces IL-8 production in gastric epithelial cells via the β1 integrin receptor

Helicobacter pylori is associated with gastrointestinal disease, most notably gastric cancer. Cytotoxin-associated antigen A (CagA) is an important virulence factor for H. pylori and causes host cells to release inflammatory factors, particularly interleukin-8 (IL-8). The mechanism by which C-terminal CagA induces IL-8 production has been studied extensively, but little is known about the role of the N-terminus.

We investigated the effect of a peptide in the N-terminal of CagA called CagA_303–456aa on IL-8 production by gastric epithelial cells, and showed that residues 303–456 of the N-terminal region of CagA induce IL-8 production via a CagA_303-456–ITGB1–p38–IL-8 pathway.