Mechanisms of Giardia-triggered colitis in susceptible hosts

• Applicant: Dr. Martina Spehlmann
• Subject Area: Gastroenterology
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 115589883

Inflammatory bowel diseases (IBD) are a clinically important group of chronic inflammatory diseases of the human gastrointestinal tract. Several disease susceptibility genes have been identified that increase the risk of developing IBD, but poorly understood environmental factors play a major role in determining the onset and course of the disease. Studies of a recent Giardia lamblia outbreak in Norway demonstrated that infection-related diarrheal and inflammatory symptoms can persist for years even after eradication of the parasite. My preliminary data indicate that Giardia infection can lead to the rapid onset of colitis in IL-10 deficient mice, a model of spontaneous chronic colitis. Together, these observations suggest that Giardia may be a new type of transient microbial trigger of persistent intestinal inflammation, which by itself does not cause mucosal inflammation. In the proposed research project, I will test the hypothesis that Giardia acts as a microbial trigger in colitis-prone hosts. To achieve these objectives, I will expand the initial observation in IL-10 deficient mice to other colitis models, and will address the mechanisms that govern Giardia-induced colitis, with a focus on the roles of the epithelial barrier, DC, and T cells.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Lars Eckmann