SCID NCR MICE NATURALLY INFECTED WITH HELICOBACTER-HEPATICUS DEVELOP PROGRESSIVE HEPATITIS, PROLIFERATIVE TYPHLITIS, AND COLITIS/

Hepatitis, proliferative typhlitis, and colitis were characterized in young adult and older SCID/NCr mice naturally infected with Helicobact er hepaticus. Liver lesions consisted of Kupffer, Ito, and oval cell h yperplasia along with multifocal to coalescing coagulative hepatocyte necrosis. Numerous Warthin-Starry-positive bacteria were observed in t he parenchyma, and there were minimal to mild accumulations of monocyt ic cells and neutrophils. Proliferative typhlitis was characterized by moderate to marked mucosal epithelial cell hyperplasia with mild mono cytic and neutrophilic infiltration. Minimal to mild colitis with muco sal epithelial cell hyperplasia of the colon was most marked in older mice. Comparable gastrointestinal lesions were not observed in uninfec ted control SCID/NCr mice. H. hepaticus was cultured from fetal viscer a of 2 of II pups sampled late in gestation from infected SCID/NCr fem ales, suggesting transplacental infection of H. hepaticus. As expected , most of the naturally infected SCID/NCr mice had no serum immunoglob ulin G response against H. hepaticus. These findings contrast with tho se in infected immunocompetent A/JCr mice, which develop a significant immune response to H. hepaticus associated with prominent multifocal mononuclear cell infiltrates in the liver, with only rare bacteria obs ervable at the periphery of inflammatory foci or in the biliary canali culi. The results demonstrate that chronic inflammatory and proliferat ive lesions simultaneously affecting the liver, cecum, and colon are a ssociated with natural infection of SCID/NCr mice with H. hepaticus an d that lesions are progressive with age. Concurrent infection with H. hepaticus may confound studies that have been attributed to similar le sions due to other experimental manipulations of SCID/NCr mice.