Reconstituted Human Polyclonal Plasma-derived Secretory-like IgM and IgA Maintain Barrier Function of Epithelial Cells Infected with an Enteropathogen [Immunology]

June 20th, 2014 by Longet, S., Vonarburg, C., Lotscher, M., Miescher, S., Zuercher, A., Corthesy, B.

Intravenous administration of polyclonal and monoclonal antibodies has proven 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, while a few IgM-based products are available as well. We have recently established that secretory-like IgA and IgM can be produced upon association of plasma-derived polymeric IgA and IgM with 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 pro-inflammatory 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. Altogether 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.
  • Posted in Journal of Biological Chemistry, Publications
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