Abstract
In mucosal secretions, secretory component (SC) is found either free or bound to polymeric IgA within the secretory IgA complex. SC displays numerous and various glycans, which are potential ligands for bacterial compounds. We first established that human SC (hSC) purified from colostrum (hSCcol) or produced in Chinese hamster ovary cells (hSCrec) exhibits the same lectin reactivity. Both forms bind to Clostridium difficile toxin A and functionally protect polarized Caco-2 cell monolayers from the cytopathic effect of the toxin. The interaction is mediated by glycans present on hSC and involves galactose and sialic acid residues. hSCcol and hSCrec were also shown to bind enteropathogenic Escherichia coli adhesin intimin and to inhibit its infectivity on HEp-2 cells in a glycan-dependent manner as well. SC remained operative in the context of the whole secretory IgA molecule and can therefore enhance its Fab-mediated neutralizing properties. On the contrary, hSC did not interact with three different strains of rotavirus (RF, RRV, and SA11). Accordingly, infection of target MA104 cells with these rotavirus strains was not reduced in the presence of either form of hSC tested. Although not a universal mechanism, these findings identify hSC as a microbial scavenger contributing to the antipathogenic arsenal that protects the body epithelial surfaces.
Highlights
IgA across the epithelium to the luminal side, where the complex is released through proteolytic cleavage [5]
In order to benefit from a continuous source of pure secretory component (SC) capable of replacing hSCcol that can be obtained in limited amounts only, we produced hSCrec in Chinese hamster ovary (CHO) cells
When used in in vitro and in vivo models of infection, hSCrec proved a valid tool to unravel several novel facets of the protein associated with pIgA or as a free polypeptide [7, 27, 28]
Summary
IgA (pIgA) across the epithelium to the luminal side, where the complex is released through proteolytic cleavage [5]. SIgA binds to antigen(s) and prevents their attachment to epithelial surfaces, a process known as immune exclusion. SC is constituted of five immunoglobulin-like domains decorated by carbohydrate residues, which constitute between 15 and 24% of the whole molecular mass and are dispatched among seven N-glycosylation sites of the polypeptide [9] The composition of these glycans includes bi- and triantennary or Lewis type structures constituting binding epitopes for bacterial adhesins [10]. The first evidence of such a role for SC was given by the observation that human SC (hSC) purified from colostrum binds to Clostridium difficile toxin A and limits its adherence on hamster brush border membranes [11]. Using established in vitro infection models for each pathogen tested, we evaluate the biological significance of the observed interactions in terms of protective activity, substantiating the role of SC in innate immunity
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