Host Epithelial Cell Invasion by Campylobacter jejuni: Trigger or Zipper Mechanism?

Abstract

Campylobacter jejuni, a spiral-shaped Gram-negative pathogen, is a highly frequent cause of gastrointestinal foodborne illness in humans worldwide. Clinical outcome of C. jejuni infections ranges from mild to severe diarrheal disease, and some other complications including reactive arthritis and Guillain–Barré syndrome. This review article highlights various C. jejuni pathogenicity factors, host cell determinants, and proposed signaling mechanisms involved in human host cell invasion and their potential role in the development of C. jejuni-mediated disease. A model is presented which outlines the various important interactions of C. jejuni with the intestinal epithelium, and we discuss the pro’s and con’s for the “zipper” over the “trigger” mechanism of invasion. Future work should clarify the contradictory role of some previously identified factors, and should identify and characterize novel virulence determinants, which are crucial to provide fresh insights into the diversity of strategies employed by this pathogen to cause disease.

Extracellular secretion of protease HtrA fromCampylobacter jejuniis highly efficient and independent of its protease activity and flagellum

“…The secretion of Cia proteins has been shown to require a functional fl agellar export system which acts as a type III secretion system [8,40]. The above similarity between CiaB and HtrA secretion capabilities with respect to enhancement by FCS let us therefore suggest that HtrA may follow the same secretion route as compared to CiaB.…”

“…One of the key differences between infection of humans and chickens by C. jejuni is the apparently higher number of bacteria invading epithelial cells in the human host [3]. This suggests that both bacterial adherence to and entrance of intestinal epithelial cells may be critical steps that are essential for disease development [8]. Early studies indicated that the C. jejuni fl agellar genes and motility are required for invasion of epithelial cells in vitro, and increased mucosal viscosity resulted in enhanced motility, adherence and invasion [9].…”

Campylobacter jejuniserine protease HtrA plays an important role in heat tolerance, oxygen resistance, host cell adhesion, invasion, and transmigration

“…However, a main difference between C. jejuni infection of humans and poultry is the apparently elevated number of bacteria entering epithelial cells in the human gut [2]. This led to the common view that C. jejuni adhesion to and entrance of human intestinal epithelial cells may represent critical steps, which are essential for disease development [10].…”

Campylobacter jejuniinduces extra-intestinal immune responses via toll-like-receptor-4 signaling in conventional IL-10 deficient mice with chronic colitis

“…Despite the high prevalence of C. jejuni induced disease and its distinctive socioeconomic impact, molecular and cellular events leading to campylobacteriosis are still poorly understood [9]. A very recent review article from Ó Cróinin and Backert highlighted various pathogenicity factors and host cell determinants proposed to be involved in establishing C. jejuni infection and triggering disease [10]. Mechanisms of intestinal inflammation are scarcely investigated due to a lack of suitable vertebrate models mimicking human disease.…”