Regulation of B7-H1 (PD-L1) expression by gastric epithelial cells and development of Treg cells during Helicobacter pylori infection (HUM8P.328)

• Published in: The Journal of immunology (1950) 2014-05, Vol.192 (1_Supplement), p.185-185.3
• Main Authors: Lina, Taslima, Shatha, Alzahrani, Pinchuk, Irina, Reyes, Victor
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.185.3

Helicobacter pylori (H. pylori) infects >50% of the world’s population and is linked to peptic ulcers and gastric cancer. We have previously shown that H. pylori upregulates B7-H1 expression on GEC, which, in turn, suppress T cell proliferation and induction of Treg cells in vitro, but the mechanism was unknown. Herein, we investigated the underlying mechanisms behind H. pylori-mediated upregulation of B7-H1 expression by GEC and its functional relevance to chronic infection. Using H. pylori wild type and isogenic mutant strains we showed that H. pylori requires its type 4 secretion system (T4SS) component cytotoxin associated gene A (CagA) and peptidoglycan for B7-H1 upregulation in GEC. In vivo confirmation was obtained when infection of C57BL/6 mice with H. pylori PMSS1 strain, containing a functional T4SS, but not with H. pylori SS1 strain lacking this delivery system, led to upregulation of B7-H1 expression, increased bacterial load, induction of Treg cell in the stomach and increased IL-10 in the serum. Interestingly, B7-H1 knock out mice showed less Treg cells and reduced bacterial loads. We also showed that H. pylori uses p38 MAPK pathway to upregulate B7-H1 expression in GEC. Our observations suggest that H. pylori T4SS contributes to the ability to evade immune-mediated clearance by modulating expression of B7-H1 in GEC. These observations may have important implications in vaccine efforts directed at H. pylori.