Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces

Abstract

An explanation of the principles and mechanisms involved in peaceful co-existence between animals and the huge, diverse, and ever-changing microbiota that resides on their mucosal surfaces represents a challenging puzzle that is fundamental in everyday survival. In addition to mechanical barriers and a variety of innate defense factors, mucosal immunoglobulins (Igs) provide protection by two complementary mechanisms: specific antibody activity and innate, Ig glycan-mediated binding, both of which serve to contain the mucosal microbiota in its physiological niche. Thus, the interaction of bacterial ligands with IgA glycans constitutes a discrete mechanism that is independent of antibody specificity and operates primarily in the intestinal tract. This mucosal site is by far the most heavily colonized with an enormously diverse bacterial population, as well as the most abundant production site for antibodies, predominantly of the IgA isotype, in the entire immune system. In embodying both adaptive and innate immune mechanisms within a single molecule, S-IgA maintains comprehensive protection of mucosal surfaces with economy of structure and function.

Recognition of Gram-positive Intestinal Bacteria by Hybridoma- and Colostrum-derived Secretory Immunoglobulin A Is Mediated by Carbohydrates

“…As SIgA carbohydrates harbor highly heterogeneous structures, these latter can contribute to combinatory-like, multiaffinity interactions with gut microorganisms (25). This was illustrated in neonatal mice in which antibody immunity fixed to the hapten nitrophenol protected against bacterial challenge (47).…”

“…Glycan Residues Are Involved in the Interaction between Bacteria and SIgA-Glycosylation is known to be involved in the innate defense against pathogens (25). Because SIgA and SC are highly glycosylated proteins (19,20), we performed deglycosylation cleaving all types of N-branched glycan residues bound to asparagine.…”

“…Both polymeric IgA (pIgA) and SC are heavily glycosylated (19,20); remarkably, N-and O-carbohydrate residues have already been implicated in the interaction with bacteria, participating in the protection against enteric pathogens (20 -25) either as adhesion competitors or in anchoring SIgA in the mucus to ensure optimal biological function. In face of the increasing involvement of glycans in the function of SIgA, we sought to determine their potential role in commensal binding (25,26). As substitute of natural SIgA and SC, we used nonspecific mouse hybridoma-derived SIgA, pIgA, and free SC, as well as their deglycosylated counterpart, to examine the role of carbohydrates in binding to a selection of bacteria (Lactobacillus, Bifidobacteria, Bacteroides, or Escherichia coli strain).…”

Immune Defenses againstBatrachochytrium dendrobatidis, a Fungus Linked to Global Amphibian Declines, in the South African Clawed Frog,Xenopus laevis

“…Antigens in the skin can be transported to the spleen, where an immune response involving both T cells and B cells can occur (9,14,41). In mammals and in fish, antibodies are present in mucosal secretions (10,28,31,53), but there have been no previous studies of antibodies in amphibian mucus.X. laevis was chosen as the species to investigate immunity to B. dendrobatidis because this species has been widely used as a model for studies of amphibian immunity since the 1960s (9,14,41).…”

“…Antigens in the skin can be transported to the spleen, where an immune response involving both T cells and B cells can occur (9,14,41). In mammals and in fish, antibodies are present in mucosal secretions (10,28,31,53), but there have been no previous studies of antibodies in amphibian mucus.…”