Increased numbers of mucosa-associated Escherichia coli are observed in both major inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC). With the identification of mutations in the NOD2-encoding gene in patients with CD and given the intracellular location of NOD2, the presence of pathogenic invasive bacteria could be the link between innate immune response to invasive bacteria and the development of the inflammation. Adherent-invasive E. coli (AIEC) are isolated from ileal biopsies of 36.4% of patients with ileal involvement of CD. These pathogenic E. coli colonize the intestinal mucosa by adhering to intestinal epithelial cells and are also true invasive pathogens, able to invade intestinal epithelial cells and to replicate intracellularly. AIEC strains also survive and replicate extensively within macrophages without inducing host cell death, and their high replication rates induce the secretion of large amounts of tumor necrosis factor alpha (TNF-alpha). There is also evidence suggesting that AIEC is involved in the formation of granulomas. The presence of AIEC is restricted to CD patients. Mucosa-associated E. coli in patients with UC can adhere to intestinal epithelial cells and induce the secretion of IL-8, but there is no evidence that these E. coli strains are invasive.