期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 43, 期 10, 页码 2650-2658出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201243281
关键词
Helicobacter pylori; IL-1; Inflammasome; NLRP3; NOD2
类别
资金
- National Institutes of Health [R01DK091191, R01 DK61707, R01AI06333]
- National Research Foundation of Korea
- Korean Government [NRF-2009-E00012]
- World Class Institute (WCI) program of the National Research Foundation of Korea (NRF) [WCI 2009-002]
- Ministry of Education, Science and Technology of Korea (MEST)
- program for Basic Research in Science and Engineering [2011-0002726]
- Crohn's and Colitis Foundation of America
- National Research Foundation of Korea [WCI 2009-002] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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)-1 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-1 and the production of mature IL-1 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-1 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-1 into IL-1, and IL-1 secretion. Finally, we show that mice deficient in caspase-1, IL-1, 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-1 production in H. pylori infected DCs.
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