Dynamic imaging the mucosal immune system (GutImmunoImaging)
Dynamic imaging the mucosal immune system
Start date: Jun 1, 2008,
End date: May 31, 2012
Dendritic cells (DCs) resident just beyond the epithelial cells (ECs) monolayer are able to extend dendrites from the lamina propria across ECs into the intestinal lumen to capture bacteria (1-3). During my post-doctoral studies, I visualized in vivo (1), for the first time, by two-photon (2P) intravital microscopy, the ability of intestinal DCs to project dendrites into the lumen to capture lumenal antigens. I associated this response to epithelial Toll-like receptor (TLR) triggering, providing timing and location for this phenomenon. Resident mucosal DCs are inflammatory anergic (4) and this phenotype is conferred by the mucosal EC-derived factors (5). DCs present in the upper tract, could be non-inflammatory participating to tolerogenic mechanisms. The inducible DCs actively recruited by ECs in response to lumenal bacteria, could play a role in inducing immunity against pathogens (4). These data suggest that the two types of DC extensions might play divergent roles in the intestine. Aim of this proposal is to investigate the dynamics of the intestinal immune response to bacteria using cutting edge techniques. We will proceed by analyzing immune phenotype changes after bacterial infection starting from the epithelial cells and ending with the DCs and their interaction with B and T lymphocytes. 1) We will use Laser capture microdissection to investigate the gene expression profile of ECs in response to lumenal antigens/bacteria at single cell level. 2) We will then investigate the fate of the two DC types (inducible versus constitutive) after sampling the intestinal luminal content. 3) By using intravital 2P microscopy, we will follow the interaction of antigen-loaded DCs with B and T cells. The results of this study will lead to the understanding of basic mechanisms controlling the gut homeostasis and the development of immunity to bacteria potentially involved in the development of chronic intestinal inflammation, like inflammatory bowel disease.
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