Abstract
Helicobacter bilis (Hb) causes hepatitis in some strains of inbred mice. The current study confirmed that Hb directly causes portal hepatitis in outbred gnotobiotic Swiss Webster (SW) mice, as we previously reported for conventional SW mice. Hbmonoassociated SW mice also developed mild enterocolitis, expanded gut-associated lymphoid tissue (GALT), and tertiary lymphoid tissue in the lower bowel. At 1 and 10 mo after infection, Hb-induced GALT hyperplasia exhibited well-organized, ectopic germinal centers with increased mononuclear cell apoptosis, MHC class II antigen presentation, and pronounced endothelial venule formation, consistent with features of tertiary lymphoid tissue. In the lower bowel, Hb induced mainly B220+ cells as well as CD4+ IL17+, CD4+ IFNγ+, and CD4+ FoxP3+ regulatory T cells and significantly increased IL10 mRNA expression. This gnotobiotic model confirmed that Hb causes portal hepatitis in outbred SW mice but stimulated GALT with an antiinflammatory bias. Because Hb had both anti- and proinflammatory effects on GALT, it should be considered a 'pathosymbiont provocateur' and merits further evaluation in mouse models of human disease.