Figure 2.

Simplified illustration of mucosal immunity emphasizing barrier defense strategies of vertebrates and Ciona (Reprinted and updated from [18)]. Gut epithelium represents a primary barrier of defense, governed by innate immune phenomena characterized by the secretion of mucus (that organizes as inner, compact, and firmly attached inner layer and a looser outer layer), antimicrobial peptides (AMPs), and soluble immune molecules. The secreted outer mucus layers are often colonized by diverse microorganisms, including bacteria, viruses, and fungi. In vertebrates, on the basolateral surface of the epithelium, host innate immunity consists of various proteolytic-coagulation cascades for wound-healing and microbial trapping, as well as complement defense pathways. Phagocytic cells, i.e., dendritic cells (DCs), as well as other cell types, populate this area. DCs sample luminal antigens and present them to the adaptive immune system, which includes gut-specific lymphocytes of both T and B cell lineages, thus triggering the maturation of immunity and the recruitment of additional cell types. In Ciona, a more simplified system includes an epithelial barrier, consisting of distinct epithelial lineages and the secretion of immune mediators, including AMPs and soluble immune molecules such as immunoglobulin (Ig)-like variable region-containing chitin-binding domains (VCBPs), into the lumen. The epithelium-associated mucus also consists of chitin fibers that run parallel to the epithelium and that are recognized and bound by VCBPs [via its chitin-binding domain (CBD)]; with opposing domain structures, free VCBP-C in the lumen can bind both bacteria and fungi. In the basolateral side, a distinct population of hemocytes, i.e., granular amoebocytes, resides in the laminar connective tissue. As in vertebrates, immunological competence in this area is mediated by coagulation/immobilization cascades and microbial trapping, complement defenses, antigenic sampling via pattern recognition receptors (PRRs), secretion of pro-inflammatory signaling, and recruitment of specialized hemocytes. However, as opposed to the vertebrate gut, Ciona relies on just innate immune mechanisms, without coupling them to the more specialized adaptive immune system.