PRJNA482639
Homos sapiens neutrophils with and without Helicobacter pylori infection.
Helicobacter pylori is a Gram-negative bacterium that infects the stomach of over half the global population causing a spectrum of disease including gastritis, peptic ulcers, and gastric adenocarcinoma. The infection initiates a chronic, neutrophil-dominant inflammatory response. We demonstrated that upon direct co-culture with H. pylori, human neutrophils undergo subtype differentiation characterized by profound nuclear hypersegmentation, changes in surface marker expression, and proinflammatory cytokine secretion. We further showed that neutrophil transcription and translation are required for this subtype differentiation. Due to the unique morphology of the nuclei of H. pylori-infected neutrophils and the requirement of transcription for neutrophil subtype differentiation, we examined the transcriptional profile of H. pylori-infected human neutrophils by RNA-sequencing. Freshly isolated human neutrophils from 3 donors were left uninfected for 0, 6, or 24 h or infected with Helicobacter pylori strain NCTC11637 (ATCC 43504) for 6 or 24 h before RNA was isolated. Results revealed that H. pylori induced extensive changes in neutrophil gene expression at both 6 and 24 h post-infection, with 1459 transcripts upregulated and 726 transcripts downregulated in neutrophils that had been infected for 24 h compared to neutrophils that had been aged for 24 h. Pathway analysis to probe for altered cellular functions suggested that groups of genes involved in cellular maintenance as well as cell death and survival were the most significantly altered. Additionally, there were eight H. pylori transcripts that were upregulated at 24 h post-infection versus 6 h post-infection, suggesting changes in bacterial gene expression during the course of infection. The current study provides fundamental insight into the molecular responses of human neutrophils to infection with H. pylori, and may increase our understanding of why neutrophils fail to effectively kill this common and persistent pathogen.