Coevolution of Mucosal Immunoglobulins and the Polymeric Immunoglobulin Receptor: Evidence That the Commensal Microbiota Provided the Driving Force

Figure 8

Crosstalk between the polymeric immunoglobulin receptor, secretory immunoglobulins, and the gut microbiota. The single-layered epithelium that lines the gastrointestinal tract is covered with a thick mucus layer, which physically excludes members of the resident microbiota but allows diffusion of shed components of microbial cells. Stimulation of epithelial toll-like receptors (TLRs) with microbial products engages the cytoplasmic adaptor protein MyD88 and initiates NFκB-dependent signaling pathways. Translocation of activated NFκB and other transcription factors to the nucleus enhances transcription of the PIGR gene. Activation of TLRs may also stimulate pIgR transcytosis. Polymeric Igs secreted by lamina propria plasma cells bind to pIgR on the basolateral surface of epithelial cells and are transcytosed to the apical surface along with unoccupied pIgR. Proteolytic cleavage of pIgR at the apical surface releases secretory SIg and free secretory component (SC). Binding of SIg and SC to luminal bacteria promotes association with the mucus layer and prevents direct access of bacteria to the epithelial surface. Over time, the continuous crosstalk with SIg shapes the composition of the gut microbiota. Modified from [17] under terms of author’s copyright with Nature Publishing Group.