Unveiling the Crucial Role of Type IV Secretion System and Motility of Helicobacter pylori in IL-1β Production via NLRP3 Inflammasome Activation in Neutrophils
| Autor: | Jong-Hwan Park, Ji-Yeon Park, Bo-Gwon Choi, Myoung-Won Seo, Dong-Yeon Kim, Tae-Sung Lee, Min-Kyoung Shin, Soo-Jin Yang, Min Jung Kang, Jeong-Ih Shin, Jae-Hun Ahn, Soon-Wook Kwon, Ah-Ra Jang |
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| Rok vydání: | 2020 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine bacterial motility Immunology Motility Inflammation Microbiology 03 medical and health sciences 0302 clinical medicine neutrophils NLRC4 medicine Immunology and Allergy Secretion Host factor type IV secretion system (T4SS) Innate immune system Helicobacter pylori biology Chemistry Inflammasome bacterial infections and mycoses biology.organism_classification TLR2 030104 developmental biology IL-1β TLR5 medicine.symptom lcsh:RC581-607 030215 immunology medicine.drug |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.01121 |
| Popis: | Helicobacter pylori is a gram-negative, microaerophilic, and spiral-shaped bacterium and causes gastrointestinal diseases in human. IL-1β is a representative cytokine produced in innate immune cells and is considered to be a key factor in the development of gastrointestinal malignancies. However, the mechanism of IL-1β production by neutrophils during H. pylori infection is still unknown. We designed this study to identify host and bacterial factors involved in regulation of H. pylori-induced IL-1β production in neutrophils. We found that H. pylori-induced IL-1β production is abolished in NLRP3-, ASC-, and caspase-1/11-deficient neutrophils, suggesting essential role for NLRP3 inflammasome in IL-1β response against H. pylori. Host TLR2, but not TLR4 and Nod2, was also required for transcription of NLRP3 and IL-1β as well as secretion of IL-1β. H. pylori lacking cagL, a key component of the type IV secretion system (T4SS), induced less IL-1β production in neutrophils than did its isogenic WT strain, whereas vacA and ureA were dispensable. Moreover, T4SS was involved in caspase-1 activation and IL-1β maturation in H. pylori-infected neutrophils. We also found that FlaA is essential for H. pylori-mediated IL-1β production in neutrophils, but not dendritic cells. TLR5 and NLRC4 were not required for H. pylori-induced IL-1β production in neutrophils. Instead, bacterial motility is essential for the production of IL-1β in response to H. pylori. In conclusion, our study shows that host TLR2 and NLRP3 inflammasome and bacterial T4SS and motility are essential factors for IL-1β production by neutrophils in response to H. pylori.IMPORTANCEIL-1β is a representative pro-inflammatory cytokine and is considered to be a central host factor for the development of gastric cancers. Although neutrophils have been considered to be involved in H. pylori-induced gastric inflammation, the underlying mechanism by which H. pylori triggers IL-1β production in neutrophils remains to be defined. In this study, our data suggested a critical role for the host TLR2 and NLRP3 inflammasome in IL-1β production by neutrophil during H. pylori infection. Moreover, we found the bacterial factors, T4SS and FlaA, to be essential for IL-1β production and NLRP3 activation during the course of H. pylori infection. Our current findings provide detailed molecular genetic mechanisms associated with IL-1β production in neutrophils in response to H. pylori infection, which can serve as innovative anti-inflammatory targets to reduce H. pylori-induced gastric malignancies. |
| Databáze: | OpenAIRE |
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