Mechanisms of colonization and adhesion on chicken intestinal epithelial cells by Campylobacter jejuni

• Applicant: Dr. Ingrid Hänel
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Veterinary Medical Science
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 105000383

Campylobacter (C.) jejuni is capable of producing a spectrum of disease scenarios depending on the immune status of the host, virulence determinants of the bacterium, synergy of existing microflora and the interaction of all three contributors. The exact mechanisms by which C. jejuni induces disease in humans remain unknown. The main source of human campylobacteriosis is assumed to be the consumption or handling of contaminated poultry meat products. Poultry such as chicken are frequently highly colonized with Campylobacter in an asymptomatic, commensal association. The reason for this pathological difference, whereby C. jejuni is pathogenic to humans but exists as commensal in chickens, is still unknown. Cell adherence and invasion are essential for the pathogenesis of human Campylobacter diarrhoea. The mechanisms by which Campylobacter adhere to the epithelium of the human intestine or asymptomatically colonize the avian gut are not well defined. Moreover, little is known about the host cell surface receptors that may be involved in the initial adherence of Campylobacter. The focus of this work will be the investigation of differences in C. jejuni colonization/adhesion when grown in conditions which model human or chicken intestinal tract environments, reflecting pathogenic and non-pathogenic situations, respectively. Based on a recently in our laboratory established chicken intestinal epithelial cell line we will identify factors that account for the divergent disease outcome following Campylobacter infection to better understand why Campylobacter colonizes the avian gut asymptomatically but causes enteric disease in humans. A better insight into host factors will allow a more complete understanding of the interaction between Campylobacter and the host and, eventually, may lead to improved strategies for controlling this zoonotic disease. We hypothesize that different mechanisms exist for binding to intestinal cell membranes from humans and chicken, thereby inducing differences in signal transduction of the respective eukaryotic cell. This hypothesis will be tested as follows: 2 1. Determination of the affinity of Campylobacter for human and avian intestinal cells 2. Characterization of cell receptors for adhesion on avian and human intestinal cells 3. Study of the involvement of associated signal transduction pathways to the cytoskeleton in primary chicken intestinal cells 4. Determination of effects of epidermal growth factor (EGF) on Campylobacter-host cell interaction 5. Comparison of differential expression of adhesion/colonization-associated genes of C. jejuni after infection of human or avian intestinal cells.

• DFG Programme: Research Grants