Supplementary file 1_Helicobacter pylori-induced immune priming requires type I interferon signaling.docx

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.</p>