Roles of Secretory Immunoglobulin A in Host-Microbiota Interactions in the Gut Ecosystem

Abstract

In the gastrointestinal tract (GIT), the immune system interacts with a variety of microorganisms, including pathogens as well as beneficial symbionts that perform important physiological functions for the host and are crucial to sustain intestinal homeostasis. In normal conditions, secretory immunoglobulin A (SIgA) is the principal antibody produced by B cells in the GIT mucosa. Polyreactivity provides certain SIgA molecules with the ability of binding different antigens in the bacterial surface, such as O-antigens and teichoic acids, while cross-species reactivity allows them to recognize and interact with different types of bacteria. These functions may be crucial in allowing SIgA to modulate the complex gut microbiota in an efficient manner. Several studies suggest that SIgA can help with the retention and proliferation of helpful members of the gut microbiota. Gut microbiota alterations in people with IgA deficiency include the lack of some species that are known to be normally coated by SIgA. Here, we discuss the different ways in which SIgA behaves in relation to pathogens and beneficial bacteria of the gut microbiota and how the immune system might protect and facilitate the establishment and maintenance of certain gut symbionts.

Keywords: cross-species reactivity; gut microbiota; immune system; microbiome; secretory IgA.

Figure 1

Secretory immunoglobulin A (SIgA) may favor the retention of beneficial members of the gut microbiota and the clearance of opportunistic pathogens through different modes of binding. Fab-dependent (canonical) binding may serve mainly to control microbiota members that may act as opportunistic pathogens, avoiding their penetration into the mucus. On the other hand, noncanonical binding may support the establishment of Bacteroides and Gram-positive symbionts in the mucus, maybe by contributing to the formation of a scaffold linking bacteria together and anchoring them to the underlying epithelium (Mathias and Corthésy, 2011). Nevertheless, direct interaction between epithelial cells and bacteria is prevented, avoiding an aggressive response by the immune system. Extracellular and intracellular receptors in epithelial cells recognize metabolites released by the gut microbiota, triggering the NFκB pathway and inducing an increased phosphorylation of tight junction proteins.

Figure 2

Secretory immunoglobulin A-microbiota interactions may differ depending on the host’s life stage. (A) In early childhood, possibly up to around 3 years of age, polyreactive SIgAs in germline configuration may dominate, cross-reacting through low to moderate affinity canonical binding. (B) In adults, somatic mutations undergone throughout life confer to SIgA the ability to recognize specific epitopes with high affinity, providing better recognition and containment of microbiota members that may act as opportunistic pathogens. Cross-species reactivity may continue through binding of conserved epitopes shared across species.