Helicobacter pylori-infected primary human monocytes display enhanced immune response to LPS

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Description

The gram-negative pathogen Helicobacter pylori infects approximately 50 per cent of the world’s human population and represents a significant risk factor for gastric ulcer and stomach cancer development. By successful co-evolution with its host and development of unique adaptive strategies, H. pylori infection leads to persistent colonization of the gastric mucosa and to chronic inflammation. Innate immune cells infiltrate the inflamed epithelium and secrete pro-inflammatory mediators and chemotactic molecules, further exacerbating the condition and leading to even more immune cell influx. This vicious cycle leads to disruption of epithelial homeostasis and continuous presence of activated immune cells in the gastric epithelium. In the present study, we characterized the initial inflammatory response of monocytes to H. pylori and additionally addressed the question, whether contact with H. pylori induces formation of innate immune memory, such as tolerance or training, in these cells. Accordingly, we demonstrate that repeated stimulation with H. pylori spaced 24 hours apart resulted in a blunted secondary inflammatory response, suggesting induction of tolerance to the pathogen itself. Infection with H. pylori followed by subsequent challenge with Escherichia coli lipopolysaccharide (LPS), however, resulted in a potentiated response to LPS in comparison to LPS stimulation of naïve monocytes. This hyper-responsiveness to LPS was only observed in monocytes stimulated with live H. pylori, whereas heat-killed bacteria did not lead to more pronounced response to LPS challenge. We could further determine that these functional adaptations of monocytes are of time-restricted nature, since the cells lose their enhanced responsiveness to LPS when challenge occurs several days after the primary stimulus. Our findings suggest that monocytes acquire a more reactive phenotype in the hours after initial contact with H. pylori, thereby potentially contributing to inflammation-associated tissue degeneration and eventual development of gastric neoplasms.
Period6 Jul 20229 Jul 2022
Event title16th World Immune Regulation Meeting 2022
Event typeConference
LocationDavos, SwitzerlandShow on map
Degree of RecognitionInternational

Fields of Science and Technology Classification 2012

  • 106 Biology