The role of CEACAM-recognition for mucosal colonization by bacterial pathogens

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Colonization of mucosal surfaces is a key step in the pathogenesis of several microbes. While the pathogens contact the epithelial surface by specific adhesins, the infected cells can respond to the bacterial challenge by detaching from the underlying tissue, a process referred to as exfoliation. How bacteria overcome the exfoliation response of mucosal epithelia is unknown. We have previously observed that contact of human epithelial cells with several pathogenic bacteria leads to enhanced integrin activity and substrate-binding of the infected eukaryotic cells preventing their detachment from the extracellular matrix in vitro. This host response depends on the presence of human CEA-related cell adhesion molecules (CEACAMs) on the eukaryotic cells as well as CEACAM-binding adhesins on the side of the bacteria and requires CEACAM-initiated de novo expression of CD105. In this research proposal we will dissect the molecular mechanism that links CD105 expression to the regulation of integrin activity. Furthermore, we will apply a newly established humanized mouse model to evaluate the extent of epithelial exfoliation in the face of bacterial CEACAM engagement, CD105 expression, and increased integrin activity in vivo. Accordingly, these investigations will not only explore integrin activity regulation, but will provide a substantial and completely novel contribution to our understanding of mucosal colonization by human-specific bacterial pathogens.