title: Mannose-containing oligosaccharides of non-specific human secretory immunoglobulin A mediate inhibition of Vibrio cholerae biofilm formation.
abstract: The role of antigen-specific secretory IgA (SIgA) has been studied extensively, whereas there is a limited body of evidence regarding the contribution of non-specific SIgA to innate immune defenses against invading pathogens. In this study, we evaluated the effects of non-specific SIgA against infection with Vibrio cholerae O139 strain MO10 and biofilm formation. Seven day old infant mice deficient in IgA (IgA(-/-) mice) displayed significantly greater intestinal MO10 burden at 24 hr post-challenge when compared to IgA(+/+) pups. Importantly, cross-fostering of IgA(-/-) pups with IgA(+/+) nursing dams reversed the greater susceptibility to MO10 infection, suggesting a role for non-specific SIgA in protection against the infection. Since biofilm formation is associated with virulence of MO10, we further examined the role of human non-specific SIgA on this virulence phenotype of the pathogen. Human non-specific SIgA, in a dose-dependent fashion, significantly reduced the biofilm formation by MO10 without affecting the viability of the bacterium. Such an inhibitory effect was not induced by human serum IgA, IgG, or IgM, suggesting a role for the oligosaccharide-rich secretory component (SC) of SIgA. This was supported by the demonstration that SIgA treated with endoglycosidase H, to cleave the high-mannose containing terminal chitobiose residues, did not induce a reduction in biofilm formation by MO10. Furthermore, the addition of free mannose per se, across a wide dose range, induced significant reduction in MO10 biofilm formation. Collectively, these results suggest that mannose containing oligosaccharides within human non-specific secretory IgA can alter important virulence phenotypes of Vibrio cholerae such as biofilm formation, without affecting viability of the microorganism. Such effects may contribute significantly to innate immune defenses against invading pathogens in vivo in the gastrointestinal tract.
authors.affiliation: South Texas Center for Emerging Infectious Diseases, Department of Biology, San Antonio, Texas, United States of America.
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
authors.forename: Bharat K R
authors.initials: BK
authors.lastname: Chaganty
authors.forename: Ty
authors.initials: T
authors.lastname: Troutman
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.forename: Syed Khalid
authors.initials: SK
authors.lastname: Ali
authors.forename: Crystal M
authors.initials: CM
authors.lastname: Lauriano
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D005260:Female; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008358:Mannose; D051379:Mice; D008892:Milk / Q000737:chemistry; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology*; D014734:Vibrio cholerae / Q000187:drug effects / Q000502:physiology*
chemical_list: D007071:Immunoglobulin A, Secretory; D009844:Oligosaccharides; D008358:Mannose