Helicobacter-induced inflammatory bowel disease in IL-10- and T cell-deficient mice

Abstract

Inflammatory bowel disease (IBD) is thought to result from a dysregulated mucosal immune response to luminal microbial antigens, with T lymphocytes mediating the colonic pathology. Infection with Helicobacter spp has been reported to cause IBD in immunodeficient mice, some of which lack T lymphocytes. To further understand the role of T cells and microbial antigens in triggering IBD, we infected interleukin (IL)-10(-/-), recombinase-activating gene (Rag)1(-/-), T-cell receptor (TCR)-alpha(-/-), TCR-beta(-/-), and wild-type mice with Helicobacter hepaticus or Helicobacter bilis and compared the histopathological IBD phenotype. IL-10(-/-) mice developed severe diffuse IBD with either H. bilis or H. hepaticus, whereas Rag1(-/-), TCR-alpha(-/-), TCR-beta(-/-), and wild-type mice showed different susceptibilities to Helicobacter spp infection. Proinflammatory cytokine mRNA expression was increased in the colons of Helicobacter-infected IL-10(-/-) and TCR-alpha(-/-) mice with IBD. These results confirm and extend the role of Helicobacter as a useful tool for investigating microbial-induced IBD and show the importance, but not strict dependence, of T cells in the development of bacterial-induced IBD.

Enterohepatic Helicobacter other than Helicobacter pylori

“…Thus, H. pullorum, H cinaedi, H. canis, H. bilis and H. muridarum have been described as responsible for this type of condition in poultry and domestic animals (4). In humans, these microorganisms have been detected by PCR in stools of patients with acute gastroenteritis (8,(71)(72)(73)(74)(75) and have been related with cases of Meckel´s diverticulum (76)(77)(78), acute appendicitis (79) and with inflammatory bowel disease (80)(81)(82)(83)(84)(85).…”

“…Due to the participation of the genetic and environmental factors, among them microbiological ones, in the pathogenesis of inflammatory bowel disease (IBD), the possible influence of these microorganisms in its development was postulated. It had been demonstrated in the laboratory that bacteria of the Helicobacter genus would produce IBD in immunodepressed mice (85), so that its presence in human patients suffering IBD was also studied. The results of the studies on this relation are heterogeneous.…”

Bacterial Infection of Smad3/Rag2 Double-Null Mice with Transforming Growth Factor-β Dysregulation as a Model for Studying Inflammation-Associated Colon Cancer

“…Mice were determined to be Helicobacter-free until infected with Helicobacter with infection confirmation by a modified fecal PCR procedure. 15 Animals were fed irradiated Picolab Rodent Diet 20 no. 5053 (breeders; PMI Nutrition International, Brentwood, MO) or autoclaved Rodent Chow no.…”

“…15 Tumors were classified according to Boivin and colleagues 18 and a tumor burden score assigned based on frankly invasive neoplasms (ie, invasion of neoplastic crypts into and beyond the tunica muscularis). By definition, herniation into the submucosa was not included in this score nor was carcinoma in situ.…”

Activated MHC-mismatched T helper-1 lymphocyte infusion enhances GvL with limited GvHD

“…Hematoxylin and eosin staining was done at the University of Arizona's University Animal Care Pathology Services Laboratory and blindly scored by a veterinary pathologist. Proximal and distal colons were scored separately for mucosal proliferation and inflammation and extent of dysplasia as previously described, 17 and the sum was considered the score for the entire colon.…”