title: Reconstituted human polyclonal plasma-derived secretory-like IgM and IgA maintain the barrier function of epithelial cells infected with an enteropathogen.
abstract: Intravenous administration of polyclonal and monoclonal antibodies has proven to be a clinically valid approach in the treatment, or at least relief, of many acute and chronic pathologies, such as infection, immunodeficiency, and a broad range of autoimmune conditions. Plasma-derived IgG or recombinant IgG are most frequently used for intravenous or subcutaneous administration, whereas a few IgM-based products are available as well. We have established recently that secretory-like IgA and IgM can be produced upon association of plasma-derived polymeric IgA and IgM with a recombinant secretory component. As a next step toward potential future mucosal administration, we sought to unravel the mechanisms by which these secretory Igs protect epithelial cells located at the interface between the environment and the inside of the body. By using polarized epithelial Caco-2 cell monolayers and Shigella flexneri as a model enteropathogen, we found that polyspecific plasma-derived SIgA and SIgM fulfill many protective functions, including dose-dependent recognition of the antigen via formation of aggregated immune complexes, reduction of bacterial infectivity, maintenance of epithelial cell integrity, and inhibition of proinflammatory cytokine/chemokine production by epithelial cells. In this in vitro model devoid of other cellular or molecular interfering partners, IgM and secretory IgM showed stronger bacterial neutralization than secretory IgA. Together, these data suggest that mucosally delivered antibody preparations may be most effective when combining both secretory-like IgA and IgM, which, together, play a crucial role in preserving several levels of epithelial cell integrity.
authors.affiliation: From the R&D Laboratory of the Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, 1011 Lausanne, Switzerland and.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Longet
authors.affiliation: CSL Behring AG, Wankdorfstrasse 10, 3000 Bern 22, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Vonarburg
authors.affiliation: CSL Behring AG, Wankdorfstrasse 10, 3000 Bern 22, Switzerland.
authors.forename: Marius
authors.initials: M
authors.lastname: Lötscher
authors.affiliation: CSL Behring AG, Wankdorfstrasse 10, 3000 Bern 22, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Miescher
authors.affiliation: CSL Behring AG, Wankdorfstrasse 10, 3000 Bern 22, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Zuercher
authors.affiliation: From the R&D Laboratory of the Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, 1011 Lausanne, Switzerland and CSL Behring AG, Wankdorfstrasse 10, 3000 Bern 22, Switzerland blaise.corthesy@chuv.ch.
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthésy
mesh_terms: D018938:Caco-2 Cells; D018925:Chemokines / Q000378:metabolism; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D006706:Homeostasis; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D018613:Microscopy, Confocal; D012763:Shigella flexneri / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence
chemical_list: D018925:Chemokines; D016207:Cytokines; D007070:Immunoglobulin A; D007075:Immunoglobulin M
keywords: Cell Invasion; Chemokine; Confocal Microscopy; Cytokine Induction; Epithelial Cell; Host-Pathogen Interaction