title: Bovine macrophages sense Escherichia coli Shiga toxin 1.
abstract: Shiga toxin (Stx)-producing Escherichia coli (STEC) infections in cattle are asymptomatic; however, Stx impairs the initiation of an adaptive immune response by targeting bovine peripheral and intraepithelial lymphocytes. As presumptive bovine mucosal macrophages (Mø) are also sensitive to Stx, STEC may even exert immune modulatory effects by acting on steps preceding lymphocyte activation at the Mø level. We therefore studied the expression of the Stx receptor (CD77), cellular phenotype and functions after incubation of primary bovine monocyte-derived Mø with purified Stx1. A significant portion of bovine Mø expressed CD77 on their surface, with the recombinant B-subunit of Stx1 binding to >50% of the cells. Stx1 down-regulated significantly surface expression of CD14, CD172a and co-stimulatory molecules CD80 and CD86 within 4 h of incubation, while MHC-II expression remained unaffected. Furthermore, incubation of Mø with Stx1 increased significantly numbers of transcripts for IL-4, IL-6, IL-10, IFN-γ, TNF-α, IL-8 and GRO-α but not for IL-12, TGF-β, MCP-1 and RANTES. In the course of bovine STEC infections, Stx1 appears to induce in Mø a mixed response pattern reminiscent of regulatory Mø, which may amplify the direct suppressive effect of the toxin on lymphocytes.
authors.affiliation: Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig University, Gießen, Germany christian.menge@fli.bund.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Menge
authors.affiliation: Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig University, Gießen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Loos
authors.affiliation: Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig University, Gießen, Germany.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Bridger
authors.affiliation: Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig University, Gießen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Barth
authors.affiliation: Royal Veterinary College, Department of Pathology and Pathogen Biology, Hatfield, UK.
authors.forename: Dirk
authors.initials: D
authors.lastname: Werling
authors.affiliation: Institute of Hygiene and Infectious Diseases of Animals, Justus-Liebig University, Gießen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Baljer
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008214:Lymphocytes / Q000382:microbiology / Q000502:physiology; D008264:Macrophages / Q000382:microbiology / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics; D022622:Shiga Toxin 1 / Q000378:metabolism*; D014281:Trihexosylceramides / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D022622:Shiga Toxin 1; D014281:Trihexosylceramides; C018549:globotriaosylceramide
keywords: Bovine monocyte-derived macrophages; CD77; Shiga toxin; enterohaemorrhagic Escherichia coli