Determinants of host-specific pathogenesis and persistence of Salmonella serovars in animals and man

While we now have a detailed knowledge of many of the virulence mechanisms of Salmonella, studies on host-specificty and disease forms for many serovars of Salmonella remains limited, in part due to the lack of infection models. Serovars which are host-adapted can also acquire a more broad host-range specificity, and known broad host-range serovars can also adapt to specific hosts. Salmonella is therefore a pathogen of variable broad and restricted host-specificity. The zoonotic potential lies in the high adaptability of this pathogen.
Recent studies suggest that differences in host responses also play a decisive role in the ability for certain serovars to establish infections in a host-specific manner. While macrophage play a large role in both antigen presentation and clearance functions of intestinal pathogens, the initial infection by Salmonella spp. is generally associated with intestinal epithelial cells, which are also capable of immune cell signalling. The host-specific immune response is therefore likely to play a large role in the outcome of infection in human and different animal species.
We are investigating the species-specific differences in the innate immune response to different bacterial serovars by comparing the functions of human, mouse and swine immune response regulators to Salmonella infections. In addition to phenotypic characterization of adhesion, invasion and intracellular growth of Salmonella serovars with different host species, microarray studies of host gene expression patterns are also being performed after infection of epithelial and macrophage cell lines of different human and animal origins. Differences in host cell responses are being determined in an effort to identify the basis for the differences in the ability for certain Salmonella serovars to persist and/or induce an effective immune response.

Co-workers:

Dr. Karsten Tedin, Nicole Walk

Grants and Funding:

- Bundesministerium für Bildung und Forschung (BMBF) Grant "Zoonose"
- H. Wilhelm Schaumann Stiftung

Collaboration:

- Dr. Dana Philpott, Department of Immunology, University of Toronto, Toronto, Canada
- Dr. Stephen Girardin, Department of Immunology, University of Toronto, Toronto, Canada

 

Selected publications:

Girardin, S.E., I.G. Boneca, L.A.M. Carneiro, A. Antignac, M. Jéhanno, J. Viala, K. Tedin, M.-K. Taha, A. Labigne, U. Zähringer, A.J. Coyle, P.S. DiStefano, J. Bertin, P.J. Sansonetti and D.J. Philpott. (2003) Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science 300:1584-1587.

 

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