The mucosal immune system comprises the largest part of the entire immune system, and the mucosal surface represents the primary site of entry for pathogenic agents. Secretory IgA (SIgA) has long been recognized as the first line of defense in protecting the intestinal epithelium from enteric pathogens and toxins. While intestinal microfold (M) cells are the primary pathway for delivery of SIgA to the gut-associated lymphoid tissue, the dectin-1 receptor plays an important role in the uptake progress of SIgA by M cells. Therefore, Dectin-1 has a huge impact on immune and homeostatic regulation, especially in the antifungal immune responses as well as other autoimmune diseases.
Introduction of Dectin-1
Dectin-1 is a C-type lectin-like receptor that was discovered to bind β-1,3-glucans and mycobacteria as well as an endogenous ligand present on T-cells. Dectin-1 contains a single extracellular C-type lectin-like domain, which is involved in calcium-independent ligand interactions, connected to a single-pass transmembrane domain by a stalk region. Attached to the cytoplasmic end of the transmembrane region lays a small intracellular tail of the Dectin-1.
Fig.1 A graphic exemplification of Dectin-1 structure (left) and downstream antifungal actions of Dectin-1 (right). (Kalia, 2021)
Function of Dectin-1
Through the recognition of β-glucans, Dectin-1 binds several fungal species such as Aspergillus, Candida, Coccidioides, Penicillium, Pneumocystis, and Saccharomyces, and because of this, focus on the immunological role for Dectin-1 has been directed at fungal immunity. Recognition of β-glucans by Dectin-1 triggers an effective immune response, including phagocytosis and proinflammatory factor production, to eliminate infecting fungi. In addition, dectin-1 is involved in the adaptive immune response as well as autoimmune diseases and immune tolerance.
SIgA-Dectin-1 Interactions
SIgA antibodies are secreted into the gut lumen and are considered to be the first line of defense in protecting the intestinal epithelium from gut pathogens. SIgA patrols the mucus and is usually known to help immune tolerance via entrapping dietary antigens and microorganisms and other mechanisms. SIgA, in complex with its antigens, can also be taken back up by the intestinal epithelium in a process known as reverse transcytosis. SIgA can thereby promote the uptake and delivery of antigens from the intestinal lumen to the Gut-Associated Lymphoid Tissues, influencing inflammatory responses. This reverse transcytosis of SIgA is mediated by specialized epithelial M cells. Dectin-1 acts as the key receptor for M cell-mediated reverse transcytosis of SIgA complexes.
Fig.2 Colocalization of SIgA-Cy3 with the Dectin-1 receptor. (Rochereau, 2013)
While the mechanism of Dectin-1 involved in the immune response against infection is generally clear, Dectin-1 is regarded as a key target for the specific delivery of novel mucosal vaccines due to its binding activity of SIgA complex, which represents an important aspect of mucosa vaccine strategy. If you are interested in Dectin-1 research or other fields in therapeutic antibody development, please feel free to contact us.
References
- Kalia, N.; et al. The role of dectin-1 in health and disease. Immunobiology. 2021, 226(2), 152071.
- Rochereau, N.; et al. Dectin-1 is essential for reverse transcytosis of glycosylated SIgA-antigen complexes by intestinal M cells. PLoS biology. 2013, 11(9), e1001658.
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