AUTHOR=Jang Ah-Ra , Kang Min-Jung , Shin Jeong-Ih , Kwon Soon-Wook , Park Ji-Yeon , Ahn Jae-Hun , Lee Tae-Sung , Kim Dong-Yeon , Choi Bo-Gwon , Seo Myoung-Won , Yang Soo-Jin , Shin Min-Kyoung , Park Jong-Hwan 

TITLE=Unveiling the Crucial Role of Type IV Secretion System and Motility of Helicobacter pylori in IL-1β Production via NLRP3 Inflammasome Activation in Neutrophils

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01121

DOI=10.3389/fimmu.2020.01121

ISSN=1664-3224

ABSTRACT=<p><italic>Helicobacter pylori</italic> 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 <italic>H. pylori</italic> infection is still unknown. We designed this study to identify host and bacterial factors involved in regulation of <italic>H. pylori</italic>-induced IL-1β production in neutrophils. We found that <italic>H. pylori</italic>-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 <italic>H. pylori</italic>. Host TLR2, but not TLR4 and Nod2, was also required for transcription of NLRP3 and IL-1β as well as secretion of IL-1β. <italic>H. pylori</italic> lacking <italic>cagL</italic>, a key component of the type IV secretion system (T4SS), induced less IL-1β production in neutrophils than did its isogenic WT strain, whereas <italic>vacA</italic> and <italic>ureA</italic> were dispensable. Moreover, T4SS was involved in caspase-1 activation and IL-1β maturation in <italic>H. pylori</italic>-infected neutrophils. We also found that FlaA is essential for <italic>H. pylori</italic>-mediated IL-1β production in neutrophils, but not dendritic cells. TLR5 and NLRC4 were not required for <italic>H. pylori</italic>-induced IL-1β production in neutrophils. Instead, bacterial motility is essential for the production of IL-1β in response to <italic>H. pylori</italic>. 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 <italic>H. pylori</italic>.</p>