title: Modulation of the CD4+ T-cell response by Helicobacter pylori depends on known virulence factors and bacterial cholesterol and cholesterol α-glucoside content.
abstract: Helicobacter pylori blocks the proliferation of human CD4(+) T cells, facilitated by vacuolating exotoxin (VacA) and γ-glutamyl transpeptidase (GGT). H. pylori-triggered T-cell reactions in mice correlate with bacterial cholesterol and cholesterol α-glucoside content but their role in human cells is unclear. We characterized the effect of VacA, GGT, and cholesterol on T-helper 1, T-helper 2, T-regulatory and T-helper 17 associated cytokines and T-cell proliferation. VacA, GGT, and bacterial cholesterol content exhibited differential and synergistic inhibitory effects on the expression of activation markers CD25 and CD69 and on interleukin 2, interleukin 4, interleukin 10, and interferon γ production. These factors did not affect the H. pylori-mediated abrogation of transforming growth factor β secretion or increased interleukin 6 production. Cholesterol α-glucosyltransferase-deficient bacteria exerted strongly reduced antiproliferative effects on primary human CD4(+) T cells. In conclusion, H. pylori shapes rather than suppresses human CD4(+) T-cell responses, and glucosylated cholesterol is a relevant bacterial component involved in this modulation.
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Macarena
authors.initials: M
authors.lastname: Beigier-Bompadre
authors.forename: Verena
authors.initials: V
authors.lastname: Moos
authors.forename: Elena
authors.initials: E
authors.lastname: Belogolova
authors.forename: Kristina
authors.initials: K
authors.lastname: Allers
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
authors.forename: Yuri
authors.initials: Y
authors.lastname: Churin
authors.forename: Ralf
authors.initials: R
authors.lastname: Ignatius
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
authors.forename: Toni
authors.initials: T
authors.lastname: Aebischer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D037181:Lectins, C-Type / Q000032:analysis; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000276:immunology / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001426:Bacterial Proteins; D002784:Cholesterol; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D037521:Virulence Factors; D005723:gamma-Glutamyltransferase; D000099192:CD69 Antigens; C508017:IL2RA protein, human; C074689:VacA protein, Helicobacter pylori; C027578:cholesteryl glucoside