Helicobacter pylori γ‐glutamyltranspeptidase impairs T‐lymphocyte function by compromising metabolic adaption through inhibition of cMyc and IRF4 expression. (30th August 2014)

• Record Type: Journal Article
• Authors: Wüstner, Stefanie; Mejías‐Luque, Raquel; Koch, Maximilian F.; Rath, Eva; Vieth, Michael; Sieber, Stephan A.; Haller, Dirk; Gerhard, Markus
• Is Part Of: Cellular microbiology. Volume 17:Number 1(2015:Jan.)
• Page Start: 51
• Page End: 61
• Publication Date: 2014-08-30
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12335
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>H</italic> <italic>elicobacter pylori</italic> (<italic>H</italic>. <italic>pylori</italic>) is a human‐specific pathogen that has evolved to cope with the immune response elicited against the infection. We previously reported that <italic>H</italic>. <italic>pylori</italic> γ‐glutamyltranspeptidase (gGT) impairs T‐lymphocyte proliferation and thus might act as immune regulatory factor. In this study, we analysed the underlying mechanism and its implications for <italic>H</italic>. <italic>pylori</italic> persistence. We found that <italic>H</italic>. <italic>pylori</italic> gGT compromised T‐cell proliferation, activation and effector cytokine expression by specifically depriving the extracellular space of glutamine. When assessing signalling cascades and transcription factors affected by <italic>H</italic>. <italic>pylori</italic> gGT, we found that expression of cMyc and IRF4, both required for metabolic adaptation of T‐lymphocytes, was highly sensitive to extracellular glutamine levels and downregulated upon gGT treatment. Moreover, we could confirm decreased IRF4 expression in T‐lymphocytes infiltrating the stomach of infected individuals. Thus, our results suggest that <italic>H</italic>. <italic>pylori</italic> gGT‐mediated glutamine deprivation in the gastric mucosa may suppress T‐cell function thereby contributing to bacterial persistence.</p> </abstract>