Helicobacter pylori-induced immune priming requires type I interferon signaling
- 1Department of Biosciences and Medical Biology, Paris-Lodron University Salzburg , ,
- 2Life Sciences Center Salzburg (LSCS) , ,
Abstract
Helicobacter pylori ( H. pylori ) infection induces persistent colonization and chronic inflammation, yet the mechanisms by which bacterial exposure establishes sustained inflammatory responses remain incompletely understood. We previously demonstrated that priming human monocytes with viable, but not heat-killed H. pylori , establishes immune priming, characterized by a heightened response to subsequent LPS challenge. Here, we delineate the signaling pathways that establish this inflammatory adaptation. Unbiased whole-cell proteomics identified type I and type II interferon (IFN) signaling as the dominant pathways distinguishing monocytes exposed to viable versus heat-killed bacteria. Consistently, viable H. pylori , but not heat-killed or PFA-inactivated bacteria, activated IFN signaling and imprinted LPS hyper-responsiveness. Manipulating IFN signaling at the time of LPS challenge did not modify this hypersensitivity, whereas blocking type I IFN signaling during priming markedly attenuated the hyperresponsiveness. Accordingly, supplementation with type I, but not type II IFN, during priming restored hypersensitivity in monocytes exposed to PFA-inactivated H. pylori . Interestingly, type I IFN only partially restored LPS-hypersensitivity in monocytes exposed to heat-killed H. pylori , indicating that heat inactivation interferes with additional signaling cues derived from intact bacteria, which are required to drive the full hyper-responsiveness to LPS. Collectively, our findings identify type I IFN as a central regulator of H. pylori -induced immune priming and reveal a previously unrecognized mechanism by which H. pylori infection programs persistent inflammatory adaptation in host immune cells through type I IFN signaling.
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BibTeX
@article{rao2026helicobacter,
title = {{Helicobacter pylori-induced immune priming requires type I interferon signaling}},
author = {Zhigang Rao and Christof Regl and Theresa Neuper and Hieu-Hoa Dang and Gunda Ueblagger and Andreas Völkerer and Christian G. Huber and Jutta Horejs-Hoeck},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1942802},
url = {https://europepmc.org/article/PMC/PMC13672020},
note = {CC BY},
}
RIS
TY - JOUR
TI - Helicobacter pylori-induced immune priming requires type I interferon signaling
AU - Zhigang Rao
AU - Christof Regl
AU - Theresa Neuper
AU - Hieu-Hoa Dang
AU - Gunda Ueblagger
AU - Andreas Völkerer
AU - Christian G. Huber
AU - Jutta Horejs-Hoeck
PY - 2026
DA - 2026/10/02
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1942802
UR - https://europepmc.org/article/PMC/PMC13672020
AB - Helicobacter pylori ( H. pylori ) infection induces persistent colonization and chronic inflammation, yet the mechanisms by which bacterial exposure establishes sustained inflammatory responses remain incompletely understood. We previously demonstrated that priming human monocytes with viable, but not heat-killed H. pylori , establishes immune priming, characterized by a heightened response to subsequent LPS challenge. Here, we delineate the signaling pathways that establish this inflammatory adaptation. Unbiased whole-cell proteomics identified type I and type II interferon (IFN) signaling as the dominant pathways distinguishing monocytes exposed to viable versus heat-killed bacteria. Consistently, viable H. pylori , but not heat-killed or PFA-inactivated bacteria, activated IFN signaling and imprinted LPS hyper-responsiveness. Manipulating IFN signaling at the time of LPS challenge did not modify this hypersensitivity, whereas blocking type I IFN signaling during priming markedly attenuated the hyperresponsiveness. Accordingly, supplementation with type I, but not type II IFN, during priming restored hypersensitivity in monocytes exposed to PFA-inactivated H. pylori . Interestingly, type I IFN only partially restored LPS-hypersensitivity in monocytes exposed to heat-killed H. pylori , indicating that heat inactivation interferes with additional signaling cues derived from intact bacteria, which are required to drive the full hyper-responsiveness to LPS. Collectively, our findings identify type I IFN as a central regulator of H. pylori -induced immune priming and reveal a previously unrecognized mechanism by which H. pylori infection programs persistent inflammatory adaptation in host immune cells through type I IFN signaling.
SN - 1664-3224
ER -