Helicobacter pylori Membrane Vesicles Stimulate Innate Pro- and Anti-Inflammatory Responses and Induce Apoptosis in Jurkat T Cells

Winter, J. ORCID: 0000-0003-3582-7596, Letley, D., Rhead, J., Atherton, J. and Robinson, K., 2014. Helicobacter pylori Membrane Vesicles Stimulate Innate Pro- and Anti-Inflammatory Responses and Induce Apoptosis in Jurkat T Cells. Infection and Immunity, 82 (4), pp. 1372-1381. ISSN 0019-9567

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Abstract

Persistent Helicobacter pylori infection induces chronic inflammation in the human gastric mucosa, which is associated with development of peptic ulceration, gastric atrophy, and gastric adenocarcinoma. It has been postulated that secretion of immunomodulatory molecules by H. pylori facilitates bacterial persistence, and membrane vesicles (MV), which have the potential to cross the gastric epithelial barrier, may mediate delivery of these molecules to host immune cells. However, bacterial MV effects on human immune cells remain largely uncharacterized to date. In the present study, we investigated the immunomodulatory effects of H. pylori MV with and without the vacuolating cytotoxin, VacA, which inhibits human T cell activity. We show a high degree of variability in the toxin content of vesicles between two H. pylori strains (SS1 and 60190). Vesicles from the more toxigenic 60190 strain contain more VacA (s1i1 type) than vesicles from the SS1 strain (s2i2 VacA), but engineering the SS1 strain to produce s1i1 VacA did not increase the toxin content of its vesicles. Vesicles from all strains tested, including a 60190 isogenic mutant null for VacA, strongly induced interleukin-10 (IL-10) and IL-6 production by human peripheral blood mononuclear cells independently of the infection status of the donor. Finally, we show that H. pylori MV induce T cell apoptosis and that this is enhanced by, but not completely dependent on, the carriage of VacA. Together, these findings suggest a role for H. pylori MV in the stimulation of innate pro- and anti-inflammatory responses and in the suppression of T cell immunity.

Item Type: Journal article
Publication Title: Infection and Immunity
Creators: Winter, J., Letley, D., Rhead, J., Atherton, J. and Robinson, K.
Publisher: American Society for Microbiology
Date: 2014
Volume: 82
Number: 4
ISSN: 0019-9567
Identifiers:
NumberType
10.1128/IAI.01443-13DOI
Rights: Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 03 Nov 2015 10:23
Last Modified: 09 Jun 2017 13:56
URI: http://irep.ntu.ac.uk/id/eprint/26103

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