Secretory immunoglobulin A carries oligosaccharide receptors for Escherichia coli type 1 fimbrial lectin

Abstract

Type 1 fimbriae with mannose-specific lectins are widely distributed among members of the family Enterobacteriaceae and confer the ability to attach to a range of host cells, including colonic epithelial cells. The mucosal surfaces are protected by secretory immunoglobulin A (IgA), which agglutinates microorganisms and prevents their attachment to host epithelial cells. This action has been attributed to a specificity of the antigen-combining site of mucosal immunoglobulins for bacterial and viral surface components. Here, we report a novel mechanism for the antibacterial effect of secretory IgA. Secretory IgA and IgA myeloma proteins, especially those of the IgA2 subclass, were shown to possess carbohydrate receptors for the mannose-specific lectin of type 1-fimbriated Escherichia coli. The presence of the high-mannose oligosaccharide chain Manal-6(Manal-3)Manxl-6(Manal-3)Man,ll-4GlcNAcIl-4GlcNAc correlated with binding activity. The interaction between bacterial mannose-specific lectins and IgA receptor oligosaccharide resulted in agglutination of the bacteria and in inhibition of bacterial attachment to colonic epithelial cells. Thus, this interaction could form the basis for a broad antibacterial function of secretory IgA against enterobacteria regardless of the specificity of antibody molecules.

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

“…Numerous such experiments clearly demonstrate protection in vivo dependent on the presence of antigen-specific IgA antibodies that interfere with pathogen adherence to or penetration through the mucosal barrier, or neutralize biologically active antigens such as viruses or toxins [41,47,48,[50][51][52][53][54]. Likewise many in vitro studies of specific antibody-mediated inhibition of bacterial adherence to epithelial cells corroborate these findings [30,[55][56][57]. However, agglutination and inhibition of the adherence of E. coli with Type 1 fimbriae to colonic epithelial cells that express a corresponding receptor can be mediated by IgA independently of specific antibody [30,58,59].…”

“…The mucosal microbiota, epithelial cells, and the mucosal immune system constitute a stable and interdependent "tripod" that maintains mucosal homeostasis by complex mechanisms [3,4,6,[24][25][26][27][28]. For example, epithelial cells display surface receptors that are selectively exploited by bacteria adhering to their apical surfaces [1,2,[28][29][30], and express the basolateral membrane receptor (polymeric Ig receptor; pIgR) that transports locally produced polymeric (p) IgA into the external secretions [23]. Bacteria 0165-2478/$ -see front matter © 2009 Elsevier B.V. All rights reserved.…”

Immunodeficiency and Mucosal Immunity

“…For example, fucose, linked α1-2 to galactose on the SC N-glycans, competes with Helicobacter pylori for binding to gastric receptors Boren et al, 1993). Free SC binds to Escherichia coli (Wold, et al, 1990;de Oliveira, et al, 2001), toxin A from Clostridium difficile (Dallas and Rolfe 1998), and both free and S-IgA-bound SC interacts specifically with a surface protein of Streptococcus pneumoniae (Hammerschmidt et al 1997;Zhang et al, 2000). These lectin capacities constitute an important mechanism by which pathogens can be prevented from adherence to epithelium.…”

“…These lectin capacities constitute an important mechanism by which pathogens can be prevented from adherence to epithelium. S-IgA also bind to type 1-fimbriated E. coli, which expresses a mannose-specific lectin (Wold et al, 1990). These bacterial binding sites on S-IgA allow IgA to participate in both innate and adaptive immunity (Royle et al, 2003).…”

Immunological Components of Milk: Formation and Function

“…Various biological activities have been attributed to the whole group of oligosaccharides (Holmgren et al, 1981) and, more recently, to individually characterized moieties, including fucosylated oligosaccharides that inhibit the hemagglutinin activity of the classical strain of Vibrio cholerae and protect against the heat-stable toxin of Escherichia coli (Newburg et al, 1990). Mannose-containing glycoproteins and glycolipids interfere with the fimbria-mediated binding of E. coli (Holmgren et al, 1987;Wold et al, 1990). The attachment of Haemophilus influenzae and Streptococcus pneumoniae to epithelial cells is inhibited by saccharides containing the disaccharide subunit Af-acetylglucosamine (l-3)-ß-galactose (Andersson et al, 1986).…”