title: Inhibition of Antigen-Specific and Nonspecific Stimulation of Bovine T and B Cells by Lymphostatin from Attaching and Effacing Escherichia coli.
abstract: Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are enteric bacterial pathogens of worldwide importance. Most EPEC and non-O157 EHEC strains express lymphostatin (also known as LifA), a chromosomally encoded 365-kDa protein. We previously demonstrated that lymphostatin is a putative glycosyltransferase that is important in intestinal colonization of cattle by EHEC serogroup O5, O111, and O26 strains. However, the nature and consequences of the interaction between lymphostatin and immune cells from the bovine host are ill defined. Using purified recombinant protein, we demonstrated that lymphostatin inhibits mitogen-activated proliferation of bovine T cells and, to a lesser extent, proliferation of cytokine-stimulated B cells, but not NK cells. It broadly affected the T cell compartment, inhibiting all cell subsets (CD4, CD8, WC-1, and γδ T cell receptor [γδ-TCR]) and cytokines examined (interleukin 2 [IL-2], IL-4, IL-10, IL-17A, and gamma interferon [IFN-γ]) and rendered T cells refractory to mitogen for a least 18 h after transient exposure. Lymphostatin was also able to inhibit proliferation of T cells stimulated by IL-2 and by antigen presentation using a Theileria-transformed cell line and autologous T cells from Theileria-infected cattle. We conclude that lymphostatin is likely to act early in T cell activation, as stimulation of T cells with concanavalin A, but not phorbol 12-myristate 13-acetate combined with ionomycin, was inhibited. Finally, a homologue of lymphostatin from E. coli O157:H7 (ToxB; L7095) was also found to possess comparable inhibitory activity against T cells, indicating a potentially conserved strategy for interference in adaptive responses by attaching and effacing E. coli.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom robin.cassady-cain@roslin.ed.ac.uk.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Cassady-Cain
authors.affiliation: The Centre for Translational and Chemical Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Blackburn
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.
authors.forename: Charlotte R
authors.initials: CR
authors.lastname: Bell
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Elshina
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.
authors.forename: Jayne C
authors.initials: JC
authors.lastname: Hope
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Stevens
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001422:Bacterial Adhesion; D001427:Bacterial Toxins / Q000276:immunology*; D002417:Cattle; D016207:Cytokines / Q000096:biosynthesis; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000276:immunology*; D054884:Host-Pathogen Interactions; D008213:Lymphocyte Activation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D029968:Escherichia coli Proteins; C406587:lymphostatin protein, E coli
keywords: Escherichia coli; adaptive; adaptive immunity; cell proliferation; host-pathogen interactions; immunity; inhibition; lymphocyte; lymphocytes; lymphostatin