CagA-dependent Hobit+ gastric tissue-resident memory T cells confer full protection from Helicobacter pylori reinfection

Gong R, Huang B, Ralser A, Friedrich V, Mibus C, Engelsberger V, Koch MR, Skerhut M, Giese T, Andrä I, Vieth M, Van Gisbergen KP, Semper RP, Gerhard M, Mejías-Luque R (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Gut BMJ Publishing Group

Article Number: gutjnl-2025-334781

DOI: 10.1136/gutjnl-2025-334781

Abstract

Background: Helicobacter pylori infection is the most prevalent bacterial infection worldwide. Attempts to develop a vaccine have not been successful, partly due to the absence of well-defined immune correlates of protection. The inflammatory response to H. pylori infection is characterised by the recruitment of T cells expressing markers of tissue-resident memory T (TRM) cells to the gastric mucosa. However, the function of TRM cells in gastric tissue during H. pylori reinfection remained poorly understood. Objective: We aimed to investigate the induction, development and function of gastric TRM cells during primary and secondary H. pylori infection. Design: We characterised gastric H. pylori-specific TRM cells in mice and humans by flow cytometry, immunohistochemistry, immunofluorescence, ChipCytometry staining and single-cell RNA sequencing. The function of gastric TRM cells was established in H. pylori eradication and reinfection experiments as well as by targeted depletion of Hobit+ TRM cells and neutrophils in mice. Results: Expression of the transcription factor Hobit governs the induction and development of gastric TRM cells, which largely depend on the presence of the H. pylori virulence factor Cytotoxin-associated gene A. H. pylori-specific CD4+ and CD8+ TRM cells resided long-term in the stomach and conferred complete protection from reinfection with the help of neutrophils. Gastric CD8+ TRM cells exhibited varying Hobit expression levels and clustered into distinct subgroups based on distinct transcriptomic and cytokine profiles, suggesting functional specialisation. Conclusion: These findings establish gastric TRM cells as bona fide correlates of protection against H. pylori, highlighting their potential for future prophylactic and therapeutic strategies.

Authors with CRIS profile

Michael Vieth Professur für Allgemeine Pathologie am Medizincampus Oberfranken

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) University of Amsterdam NL Netherlands (NL)

How to cite

APA:

Gong, R., Huang, B., Ralser, A., Friedrich, V., Mibus, C., Engelsberger, V.,... Mejías-Luque, R. (2025). CagA-dependent Hobit+ gastric tissue-resident memory T cells confer full protection from Helicobacter pylori reinfection. Gut. https://doi.org/10.1136/gutjnl-2025-334781

MLA:

Gong, Ruolan, et al. "CagA-dependent Hobit+ gastric tissue-resident memory T cells confer full protection from Helicobacter pylori reinfection." Gut (2025).

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