<i>Helicobacter pylori</i> infection delays neutrophil apoptosis and exacerbates inflammatory response

<b>Aim:</b> Understanding molecular mechanisms of <i>Helicobacter pylori</i> (<i>H. pylori</i>)-induced inflammation is important for developing new therapeutic strategies for gastrointestinal diseases. <b>Materials &amp; methods:</b> We designed an <i>H. pylori</i>-neutrophil infection model and explored the effects of <i>H. pylori</i> infection on neutrophils. <b>Results:</b><i>H. pylori</i> infected neutrophils showed a low level of apoptosis. <i>H. pylori</i> stimulation activated the NACHT/LRR/PYD domain-containing protein 3 (NLRP3)-gasdermin-D (GSDMD) pathway for interleukin (IL)-1β secretion. However, IL-1β secretion was not completely dependent on GSDMD, as inhibition of autophagy significantly reduced IL-1β release, and autophagy-related molecules were significantly upregulated in <i>H. pylori</i>-infected neutrophils. <b>Conclusion:</b> Therefore, <i>H. pylori</i> infection inhibits neutrophils apoptosis and induces IL-1β secretion through autophagy. These findings may be utilized to formulate therapeutic strategies against <i>H. pylori</i> mediated chronic gastritis. <i>Helicobacter pylori</i> (<i>H. pylori</i>) is a common opportunistic morbigenous bacterium worldwide and associated with gastrointestinal diseases. <i>H. pylori</i> strain ATCC 11637 was used in this study. We designed a <i>H. pylori</i> neutrophils infection model <i>in vitro</i> utilizing <i>in vivo</i> harvested neutrophils. Pathological tissue analysis were carried out by multiplexed immunohistochemistry. The <i>H. pylori</i> infected neutrophils showed a lower frequency of annexin V-labeling and upregulation of CXCR4. <i>H. pylori</i> stimulation promote the activation of the NLRP3-GSDMD-IL1β pathway. Autophagy inhibitor significantly reduced IL-1β release and autophagy related molecules were upregulated significantly in <i>H. pylori</i> infected neutrophils. <i>H. pylori</i> inhibited neutrophil apoptosis and prolonged neutrophil survival. The inhibition of neutrophil apoptosis by <i>H. pylori</i> was mediated by inhibition of caspase-3 activation. <i>H. pylori</i> infection induced IL-1β secretion by neutrophils via an autophagy-dependent mechanism.