Developing a novel mouse model for dissecting innate immune responses against Helicobacter pylori

• Applicant: Professorin Dr. Christine Josenhans
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280354483

The human Helicobacter pylori infection is still one of the major infectious diseases worldwide. Severe infection sequelae such as cancer, currently increasing problems with treating the infection and unsuccessful vaccine development highlight the necessity of improving our grasp of the immunological crosstalk between pathogen and host during this infection. Understanding innate immune responses against H. pylori has been hampered by a lack of suitable animal models, including a dearth of well-characterised mouse infection models. Mice, modified mice and humanized mice have been frequently used previously for experimental infection with H. pylori. However, on the bacterial side, these mouse models are not sufficiently defined to be able to draw valid conclusions concerning the role of bacterial factors in influencing the host innate immune defense against these bacteria. This lack of understanding concerns the bacterial genome content and genome integrity and their genome adaptation during the initial infection of mice. Based on our recently developed gerbil infection model with a stably adapted H. pylori strain, we would now like to make use of a similar approach to generate a novel H. pylori mouse model involving a genetically stable, mouse-adapted and well-characterized H. pylori strain. It is possible that continuous genome adaptation occurs as well during persistent colonization of the mouse, which we would like to clarify by bacterial genome sequencing in combination with functional assays. We would further use this mouse model in order to generate an in-depth characterization of innate immune responses against H. pylori wild type strains with or without the cag pathogenicity island. In the future, we would like to apply and provide this mouse model, including work in genetically modified mice, to dissect the role of bacterial factors such as the cag type IV secretion system and lipopolysaccharide in the host innate immune responses.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Saskia Catherina Stein, Ph.D.