Mannose-Containing Oligosaccharides of Non-Specific Human Secretory Immunoglobulin A Mediate Inhibition of Vibrio cholerae Biofilm Formation

Ashlesh K Murthy,Ty Troutman,Jieh-Juen Yu,Karl E Klose,Bernard P Arulanandam,Syed Khalid Ali,M Neal Guentzel,James P Chambers,Crystal M Lauriano,Bharat K R Chaganty,Joy Sturtevant

doi:10.1371/journal.pone.0016847

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 oligosacchardies 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.

Highlights

The large surface area of mucosal membranes is a major portal of entry and site for colonization by microorganisms [1]
Non-specific secretory immunoglobulin A (IgA) (SIgA) is involved in reduction of Vibrio cholerae colonization in vivo We evaluated whether SIgA could alter the phenotype of V
IgA-/- suckling infant mice cross-fostered with lactating IgA+/+ mothers displayed a significant (p#0.05) reduction (,2 log10), in intestinal bacterial burden when compared to IgA-/pups with IgA-/- dams (Fig 1B), suggesting the contribution of nonVibrio specific SIgA in milk to the control of intestinal V. cholerae infection

Summary

Introduction

The large surface area of mucosal membranes is a major portal of entry and site for colonization by microorganisms [1]. Much of the available evidence regarding the protective role of SIgA against pathogens is derived from studies of antigen-specific IgA [11]. We [13] have shown that mice deficient in pIgR displayed significantly enhanced intestinal inflammation in response to dextran sodium sulfate induced colitis. It is not clear how non-specific SIgA mediates these effects; several studies [14], including ours [13], point toward an important contribution of the secretory component (SC). More recent studies have shown the probable role of glycans on SIgA in mediating the recognition of bacterial polysaccharides in innate immune responses [15]

Methods

Results

Conclusion