Helicobacter pylori Infection Remodels Neutrophil‐Derived Extracellular Vesicles, Promoting Stress and Apoptosis in Infected Epithelial Cells
- 1Indian Institute of Technology Mandi
Abstract
Helicobacter pylori is a Gram‐negative bacterium that establishes colonization in the human stomach and is estimated to infect over half of the global population. It is recognized as a significant causative agent of chronic gastritis, peptic ulcers, and gastric cancer. Neutrophils play a central role in innate defence against H. pylori; however, dysregulated neutrophil activation contributes to epithelial injury and persistent inflammation. Here, we show that H. pylori enhance neutrophil exocytosis and stimulates the release of extracellular vehicles (EVs) with distinct biophysical and molecular characteristics. Infected neutrophils released smaller and more abundant EVs than uninfected controls. These H. pylori–induced neutrophil EVs (HPN‐EVs) suppressed PI3K/Akt signalling, increased reactive oxygen species, disrupted mitochondrial integrity, and induced cytochrome c release, caspase activation, and apoptosis in infected gastric epithelial cells. Proteomics profiling revealed enrichment of neutrophil granule proteins, particularly LL‐3, and depletion of proteins associated with cellular homeostasis. EV‐mediated LL‐37 delivery reproduced key pro‐apoptotic effects of HPN‐EVs, supporting its functional role in epithelial injury. Consistent with these findings, circulating EVs from H. pylori‐infected patients exhibited elevated LL‐37 levels and induced similar pro‐apoptotic responses. Together, these findings identify LL‐37‐enriched HPN‐EVs as important mediators of neutrophil–epithelial crosstalk and investigating EV‐associated cargo as a potential therapeutic target in H. pylori‐associated disease.
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BibTeX
@article{keshri2026helicobacter,
title = {{Helicobacter pylori Infection Remodels Neutrophil‐Derived Extracellular Vesicles, Promoting Stress and Apoptosis in Infected Epithelial Cells}},
author = {Anand Kumar Keshri and Suraj Singh Rawat and Durganand Thakur and Swati Sharma and Parul Mehra and Anubha Chaudhary and Ananaya Kapoor and Amit Prasad},
journal = {Journal of extracellular vesicles},
year = {2026},
month = nov,
doi = {10.1002/jev2.70388},
url = {https://europepmc.org/article/PMC/PMC13730263},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Helicobacter pylori Infection Remodels Neutrophil‐Derived Extracellular Vesicles, Promoting Stress and Apoptosis in Infected Epithelial Cells
AU - Anand Kumar Keshri
AU - Suraj Singh Rawat
AU - Durganand Thakur
AU - Swati Sharma
AU - Parul Mehra
AU - Anubha Chaudhary
AU - Ananaya Kapoor
AU - Amit Prasad
PY - 2026
DA - 2026/11/01
JO - Journal of extracellular vesicles
DO - 10.1002/jev2.70388
UR - https://europepmc.org/article/PMC/PMC13730263
AB - Helicobacter pylori is a Gram‐negative bacterium that establishes colonization in the human stomach and is estimated to infect over half of the global population. It is recognized as a significant causative agent of chronic gastritis, peptic ulcers, and gastric cancer. Neutrophils play a central role in innate defence against H. pylori; however, dysregulated neutrophil activation contributes to epithelial injury and persistent inflammation. Here, we show that H. pylori enhance neutrophil exocytosis and stimulates the release of extracellular vehicles (EVs) with distinct biophysical and molecular characteristics. Infected neutrophils released smaller and more abundant EVs than uninfected controls. These H. pylori–induced neutrophil EVs (HPN‐EVs) suppressed PI3K/Akt signalling, increased reactive oxygen species, disrupted mitochondrial integrity, and induced cytochrome c release, caspase activation, and apoptosis in infected gastric epithelial cells. Proteomics profiling revealed enrichment of neutrophil granule proteins, particularly LL‐3, and depletion of proteins associated with cellular homeostasis. EV‐mediated LL‐37 delivery reproduced key pro‐apoptotic effects of HPN‐EVs, supporting its functional role in epithelial injury. Consistent with these findings, circulating EVs from H. pylori‐infected patients exhibited elevated LL‐37 levels and induced similar pro‐apoptotic responses. Together, these findings identify LL‐37‐enriched HPN‐EVs as important mediators of neutrophil–epithelial crosstalk and investigating EV‐associated cargo as a potential therapeutic target in H. pylori‐associated disease.
SN - 2001-3078
ER -