IgA is the dominant immunoglobulin isotype produced in mammals, largely secreted across the intestinal mucosal surface. IgA mediates microbial homeostasis at the intestinal mucosa. Within the gut, IgA acts in a context-dependent manner to both prevent and promote bacterial colonization and to influence bacterial gene expression, thus providing exquisite control of the microbiota. Recent advances have helped to clarify the antigenic specificity and immune selection of intestinal IgA and suggested that diet and nutrition play an important role in shaping IgA recognition of the microbiota. Although the mechanism has not been totally revealed, the fascinating paradigm of IgA-microbiota homeostasis shows huge application potential. Creative Biolabs is a world-leading biotech company with skilled groups and established platforms, which was engaged in advanced therapeutic strategy development. Aimed at intestinal IgA, we have accumulated rich experience and realized remarkable goals. It is our pleasure to share our works with partners all over the world.
Introduction of IgA-microbiota Interaction
Secretory immunoglobulin A (SIgA) is the major mucosal antibody and the most abundant isotype in humans. Secreted into the intestinal lumen at the rate of several grams per day, SIgA acts both to prevent infections and to maintain homeostasis of the commensal microbiota. Unlike serum IgA, SIgA is dimeric which contains two monomers attach at their Fc regions via a joining chain. The IgA expression can occur with or without T cell help, while T cell-dependent pathways increased antigen specificity and affinity of IgA. Mucosal SIgA preferentially targets surface antigens of intact bacteria such as lipopolysaccharide, teichoic acid, and extracellular capsules. Moreover, Glycosylation of IgA itself further contributes to the recognition of bacterial glycans. Indeed, conserved bacterial epitopes, commensal superantigens, and widespread glycan reactivity lead to specific microbiota-binding patterns of intestinal IgA.
Fig.1 Generation of microbiota-reactive IgA through T cell-independent and T cell-dependent pathways. (Huus, 2021)
Function of IgA-microbiota Interaction
Similar to most antibodies, SIgA is important in containing bacteria within the gut and preventing their systemic spread. Moreover, SIgA binding can affect bacterial gene expression and epitope production at a molecular level, which contributes to the treatment of pathogen infections such as Clostridioides difficile and Salmonella.
Patients with SIgA deficiency experience a dysbiosis of the gut microbiota, which indicates SIgA can both prevent and promote bacterial colonization, depending on the type and context of the interaction. Moreover, SIgA targeting not only impacts the composition and colonization of the gut microbiota but also shapes bacterial gene expression and function, allowing IgA to shape a beneficial microbiota at a molecular level.
Given the influence of the intestinal microbiota on antibody responses, there has been substantial interest in the ability of the microbiota to modulate vaccine responsiveness. It is a matter of serious public health concern that oral vaccinations are less effective in low- and middle-income countries than in industrialized settings. The microbiota has been proposed as a potential explanatory factor for this variation.
Fig.2 Functions of IgA in the gastrointestinal tract. (Huus, 2021)
IgA-microbiota interactions are staggeringly diverse. IgA-microbiota binding shapes microbial colonization patterns in the intestine, ultimately supporting overall microbiota diversity. Moreover, IgA recognition alters bacterial epitope expression and thus functionality, providing molecular control over the motility and metabolism of the gut microbiome. If you are interested in the research of IgA-microbiota interactions, please feel free to contact us for more details.
Reference
- Huus, K. E.; et al. Diversity and dynamism of IgA−microbiota interactions. Nature Reviews Immunology. 2021, 1-12.
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