Gut · 2025
CagA-dependent Hobit+ gastric tissue-resident memory T cells confer full protection from Helicobacter pylori reinfection.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gong Ruolan, Huang Boyang, Ralser Anna, Friedrich Verena, Mibus Cora, Engelsberger Veronika, Koch Maximilian R A, Skerhut Martin, Giese Tobias, Andrä Immanuel, Vieth Michael, van Gisbergen Klaas P J M, Semper Raphaela P, Gerhard Markus, Mejías-Luque Raquel
Аннотация
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.
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.