Gastroenteritis in NF-κB-Deficient Mice Is Produced with Wild-TypeCamplyobacter jejunibut Not withC. jejuniLacking Cytolethal Distending Toxin despite Persistent Colonization with Both Strains

• DOI: 10.1128/iai.72.2.1116-1125.2004
• Publication Date: 2004-01-24T23:46:23Z
• Authors: James G. Fox; Arlin B. Rogers; Mark T. Whary; Zhongming Ge; Nancy S. Taylor; Sandy Xu; Bruce H. Horwitz; Susan E. Erdman
• Keywords: Cytolethal distending toxin; Wild type; Helicobacter

Campylobacter jejuni continues to be a leading cause of bacterial enteritis in humans. However, because there are no readily available animal models study the pathogenesis C. jejuni-related diseases, significance potential virulence factors, such as cytolethal distending toxin (CDT), vivo poorly understood. Mice deficient NF-kappaB subunits (p50(-/-) p65(+/-)) C57BL/129 background particularly susceptible colitis induced by another enterohepatic microaerobe, Helicobacter hepaticus, which, like jejuni, produces CDT. Wild-type 81-176 and an isogenic mutant lacking CDT activity (cdtB mutant) were inoculated into NF-kappaB-deficient (3X) mice. colonized 29 50% mice at 2 4 months postinfection (p.i.), respectively, whereas cdtB p.i. but none Although developed mild gastritis typhlocolitis, they had robust immunoglobulin G (IgG) Th1-promoted IgG2a humoral responses both wild-type strain mutant. In contrast, 75 100% 3X with wild type similar levels all times examined. caused moderately severe proximal duodenitis that more than gastrointestinal lesions Persistent colonization was associated significantly impaired IgG (P < 0.001), which is consistent innate or adaptive immune system defect(s). These results suggest mechanism clearance dependent may have proinflammatory vivo, well role ability escape surveillance. should useful model further other aspects pathogenesis.