Mucosal immunoglobulins

Woof, Jenny M.; Městecký, Jiří

doi:10.1111/j.0105-2896.2005.00290.x

Cited by 265 publications

(207 citation statements)

References 182 publications

(207 reference statements)

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“…Secretory Igs such as IgA, IgM, and IgG that are present in mucosal surfaces potentially provide a first line of defense against microorganisms (71). Surface proteins that bind human Ig-Fc have been identified in many strains of Streptococcus pyogenes (group A streptococcus) and group B streptococcus, two important human pathogens (72).…”

Section: Discussionmentioning

confidence: 99%

Crystal Structure of a Mucus-binding Protein Repeat Reveals an Unexpected Functional Immunoglobulin Binding Activity

MacKenzie

Tailford

Hemmings

et al. 2009

Journal of Biological Chemistry

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Lactobacillus reuteri mucus-binding protein (MUB) is a cellsurface protein that is involved in bacterial interaction with mucus and colonization of the digestive tract. The 353-kDa mature protein is representative of a broadly important class of adhesins that have remained relatively poorly characterized due to their large size and highly modular nature. MUB contains two different types of repeats (Mub1 and Mub2) present in six and eight copies, respectively, and shown to be responsible for the adherence to intestinal mucus. Here we report the 1.8-Å resolution crystal structure of a type 2 Mub repeat (184 amino acids) comprising two structurally related domains resembling the functional repeat found in a family of immunoglobulin (Ig)-binding proteins. The N-terminal domain bears striking structural similarity to the repeat unit of Protein L (PpL) from Peptostreptococcus magnus, suggesting binding in a non-immune Fab-dependent manner. A distorted PpL-like fold is also seen in the C-terminal domain. As with PpL, Mub repeats were able to interact in vitro with a large repertoire of mammalian Igs, including secretory IgA. This hitherto undetected activity is consistent with the current model that antibody responses against commensal flora are of broad specificity and low affinity. The human gastrointestinal tract (GIT)3 contains trillions of bacteria, representing hundreds of species and thousands of subspecies (1). They outnumber our own cells by a factor of 10 and contribute many physiological capabilities, including the provision of metabolic attributes not encoded in the human genome (2). A protective layer of mucus, consisting of a complex mixture of large, highly glycosylated proteins (mucins) (3), covers the epithelial cells of the intestine and offers an attachment site for the colonizing bacteria. These bacteria play important roles in maintaining normal gut function and in building resistance of the host to pathogenic micro-organisms (4, 5). Some may use mucins as their major carbon and energy source (6, 7).Lactobacilli are Gram-positive microaerophilic bacteria naturally present in the dominant colonic microbiota and have been considered to be beneficial for human health (8). They are commonly used as probiotics, which are defined by the Food and Agriculture Organization/World Health Organization as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (9). As probiotic agents, lactobacilli can prevent or alleviate infectious diarrhea through their effects on the immune system and promote host resistance to colonization by pathogens (10, 11), and many have been shown to adhere to intestinal mucus (12-19). Confirmation of this lactobacillus-mucus association has not only been observed in vitro, but has also been validated by ex vivo/in vivo microscopic analysis of biopsy samples (20,21). In most cases, lactobacilli adhesion to mucus has been proposed to be mediated by proteins (22-30). Compared with the present understanding of the adhesive mechanisms of human...

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Section: Discussionmentioning

confidence: 99%

Crystal Structure of a Mucus-binding Protein Repeat Reveals an Unexpected Functional Immunoglobulin Binding Activity

MacKenzie

Tailford

Hemmings

et al. 2009

Journal of Biological Chemistry

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“…The predominant isotype is IgA1 (*85 % of total IgA), which is consistent with the dominance of IgA1-producing plasma cells in the bone marrow. On the other hand, polymeric IgA (dimers or tetramers) predominates in external secretions [22]. The IgA1/IgA2 ratio reflects differential distribution of IgA1 and IgA2 secreting cells in corresponding mucosal tissues.…”

Section: Physiological Iga Structure and Functionmentioning

confidence: 99%

Immunoglobulin A nephropathy: a pathophysiology view

2016

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“…Briefly, 50 g of toxin A was dissolved in 200 l of 0.2 M sodium borate buffer (pH 9.0) containing 10 g of NaBH 4 […”

Section: Cells and Culture Conditions-human Colonic Adenocarcinomamentioning

confidence: 99%

“…mucus, lysozyme, defensins, and lactoferrin) and by an induced specific immune response, which mainly relies at the antibody level on the secretion of secretory IgA (SIgA) 3 (3). SIgA, the major immunoglobulin found in secretions, consists of two or four monomeric IgA linked through a J chain in association with secretory component (SC) (4). SC is derived from the polymeric immunoglobulin receptor (pIgR) that ensures selective transport of polymeric IgA (pIgA) across the epithelium to the luminal side, where the complex is released through proteolytic cleavage (5).…”

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confidence: 99%

Glycans on Secretory Component Participate in Innate Protection against Mucosal Pathogens

Perrier

Sprenger

Corthésy

2006

Journal of Biological Chemistry

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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 Fabmediated 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.

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Mucosal immunoglobulins

Cited by 265 publications

References 182 publications

Crystal Structure of a Mucus-binding Protein Repeat Reveals an Unexpected Functional Immunoglobulin Binding Activity

Crystal Structure of a Mucus-binding Protein Repeat Reveals an Unexpected Functional Immunoglobulin Binding Activity

Immunoglobulin A nephropathy: a pathophysiology view

Glycans on Secretory Component Participate in Innate Protection against Mucosal Pathogens

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