| First Author | Kim DJ | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 10 | Pages | 2650-8 |
| PubMed ID | 23818043 | Mgi Jnum | J:201678 |
| Mgi Id | MGI:5515265 | Doi | 10.1002/eji.201243281 |
| Citation | Kim DJ, et al. (2013) The Cag pathogenicity island and interaction between TLR2/NOD2 and NLRP3 regulate IL-1beta production in Helicobacter pylori infected dendritic cells. Eur J Immunol 43(10):2650-8 |
| abstractText | Helicobacter pylori colonization of the stomach affects about half of the world population and is associated with the development of gastritis, ulcers, and cancer. Polymorphisms in the IL1B gene are linked to an increased risk of H. pylori associated cancer, but the bacterial and host factors that regulate interleukin (IL)-1beta production in response to H. pylori infection remain unknown. Using murine BM-derived DCs, we show that the bacterial virulence factors cytotoxin-associated genes pathogenicity island and CagL, but not vacuolating cytotoxin A or CagA, regulate the induction of pro-IL-1beta and the production of mature IL-1beta in response to H. pylori infection. We further show that the host receptors, Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain 2 (NOD2), but not NOD1, are required for induction of pro-IL-1beta and NOD-like receptor pyrin domain containing 3 (NLRP3) in H. pylori infected DCs. In contrast, NLRP3 and the adaptor ASC were essential for the activation of caspase-1, processing of pro-IL-1beta into IL-1beta, and IL-1beta secretion. Finally, we show that mice deficient in caspase-1, IL-1beta, and IL-1 receptor, but not NLRP3, are impaired in the clearance of CagA-positive H. pylori from the stomach when compared with WT mice. These studies identify bacterial cag pathogenicity island and the cooperative interaction among host innate receptors TLR2, NOD2, and NLRP3 as important regulators of IL-1beta production in H. pylori infected DCs. |
