Transmigration route of Campylobacter jejuni across polarized intestinal epithelial cells: paracellular, transcellular or both?

Abstract

Intact intercellular junctions and cellular matrix contacts are crucial structural components for the formation and maintenance of epithelial barrier functions in humans to control the commensal flora and protect against intruding microbes. Campylobacter jejuni is one of the most important zoonotic pathogens causing food-borne gastroenteritis and potentially more severe diseases such as reactive arthritis or Guillain–Barré syndrome. Crossing the intestinal epithelial barrier and host cell invasion by C. jejuni are considered to represent the primary reasons of gut tissue damage in humans and various animal model systems including monkeys, piglets, rabbits, hamsters and ferrets. C. jejuni is also able to invade underlying tissues such as the lamina propria, can enter the bloodstream, and possibly reach distinct organs such as spleen, liver or mesenteric lymph nodes. However, the molecular mechanisms as well as major bacterial and host cell factors involved in these activities are poorly understood. Various models exist by which the pathogen can trigger its own transmigration across polarized intestinal epithelial cells in vitro, the paracellular and/or transcellular mechanism. Recent studies suggest that bacterial factors such as flagellum, serine protease HtrA and lipooligosaccharide LOS may play an active role in bacterial transmigration. Here we review our knowledge on transmigration of C. jejuni as well as some other Campylobacter species, and discuss the pros and cons for the route(s) taken to travel across polarized epithelial cell monolayers. These studies provide fresh insights into the infection strategies employed by this important pathogen.

HtrA-mediated E-cadherin cleavage is limited to DegP and DegQ homologs expressed by gram-negative pathogens

“…Those gastrointestinal bacteria colonize the epithelium of the intestine as the first barrier. E-cadherin shedding could promote bacterial virulence of these pathogens through providing entry through the polarized epithelium where specific virulence and pathogenic factors then interfere with host cell functions [31, 32]. Hence, it would be highly interesting to investigate the influence of the different HtrA homologs in their respective experimental animal models in vivo as HtrA proteins represent attractive therapeutic target molecules.…”

“…E-cadherin is an important key molecule in the establishment and maintenance of an intact epithelial barrier. Consequently, E-cadherin cleavage disrupts the barrier function and allows bacterial entry into the intercellular space and transmigration [31, 32]. In H. pylori or C. trachomatis , genomic htrA deletions mutants could not be generated so far.…”

Claudin-related intestinal diseases

“…However, the pathways of Campylobacter transmigration (trans-or paracellular or both) and how it affects the epithelial barrier are not well understood. Data on this were mostly obtained from cell cultures and animal models [79].…”

Klebsiella pneumoniae Translocates across the Intestinal Epithelium via Rho GTPase- and Phosphatidylinositol 3-Kinase/Akt-Dependent Cell Invasion

“…In the transcellular pathway, well-studied enteropathogens such as Salmonella, Shigella, Listeria, and Yersinia species invade nonphagocytic epithelial cells by subverting host cytoskeleton dynamics (20). In the paracellular pathway, bacteria such as Vibrio cholerae (21), Campylobacter jejuni (22), and Pseudomonas aeruginosa (23) perturb epithelial integrity to facilitate bacterial translocation by disrupting the cell tight junctions (TJs), the structures between epithelial cells that control paracellular permeability.…”