Intestinal Microvascular Endothelium and Innate Immunity in Inflammatory Bowel Disease: a Second Line of Defense?

Abstract

Impairment of the intestinal epithelial barrier function is presently understood to be a key pathogenic step in the initiation and development of chronic human inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC). Invasion by microbial pathogens has been proven to be a crucial event in the perpetuation of the disease process (21, 49). Limited data are available on how mucosal cellular compartments—which include local leukocyte populations as well as nonimmune cells such as fibroblasts and endothelial cells (EC)—might respond to invading enteric pathogens. In IBD, these pathogens might include adherent-invasive pathovars of Escherichia coli, which have been associated with ileal Crohn's disease involvement for some patients (20). However, studies assessing mucosal invasion should be interpreted with caution in view of the fact that enteric microbia potentially contaminate deeper mucosal layers during sampling and sectioning of tissue specimens (79). Several mechanisms of innate and adaptive immunity are thought to orchestrate the immune dysregulation causing tissue destruction and scar formation, eventually leading to clinical complications (51). Recent work has focused on EC as an active cell population involved in innate and adaptive immune responses (11, 56, 57). This review article discusses the endothelial expression of specific pathogen receptors, including the Toll-like receptor (TLR) family, in the setting of human intestinal inflammatory diseases.