ICMI 2015

T.70 Intestinal Endothelial MyD88 Signalling is Protective During Salmonella-induced Colitis

Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Ganive Bhinder , University of British Columbia, Vancouver, BC, Canada
Carly Aspden , University of Victoria, Victoria, BC, Canada
Bruce Vallance , University of British Columbia, Vancouver, BC, Canada
In recent years, mutations in several innate immune signalling pathways have been linked to an increased susceptibility of developing Inflammatory Bowel Disease (IBD). Germline defects in several of these innate pathways (MyD88, NOD2) have been shown to lead to increased susceptibility to disease1,2, however the intricacies of this susceptibility require further investigation. Currently, it is not completely understood which cell types contribute to the protective effects of MyD88 signalling, though hematopoietic and non-hematopoietic linages are likely involved3. Here we aim to examine the role of MyD88 signalling in one such non-hematopoietic cell type: endothelial cells during Salmonella-induced colitis utilizing cell type specific knockout mice (EC-MyD88-/-). The role of MyD88 signalling within endothelial cells is of interest to clarify as IBD patients often exhibit altered microvasculature in inflamed regions of the intestine4. In addition, germ-free mice do not develop the same extensive intestinal vascular networks as their conventional counterparts5, suggesting a potential role for MyD88-dependant bacterial sensing in its regulation. Overall, we aim to determine the role of endothelial-MyD88 signalling during intestinal inflammation.

EC-MyD88-/-mice exhibited significantly accelerated macroscopic and histological tissue damage at early time-points (D1-3) post-infection compared to wildtype, even though similar intestinal pathogen burdens were found. Gene expression analysis showed significant induction of several chemokines in EC-MyD88-/- mice; with immunostaining revealing increased immune cell recruitment along with significant cell death (TUNEL+ cells) within the mucosal tissue.

[1]Rakoff-Nahoum 2004 Cell 118:229-241 [2]Couturier-Maillard 2013 J Clin Invest 123:700-11 [3]Brandl 2010 PNAS 107:19967-19972  [4]Hatoum 2003 Gastroenterology 125:58-69 [5]Stappenbeck 2002 PNAS 99:15451-15455