Surfactant Protein D plays important roles in innate host defense and immune regulation. Although SP-D is secreted by lung epithelial cells, there are also many extrapulmonary sites of mucosal expression, including the gastrointestinal and genitourinary tracts. SP-D is a collagenous C-type lectin (collectin) that is usually assembled as tetramers of trimeric subunits, each with an N-terminal crosslinking domain, an uninterrupted triple helical collagen domain, and a trimeric carbohydrate recognition domain (NCRD).
Microbial ligands include viral glycans, bacterial endotoxins, mycobacterial lipoglycans, and fungal polysaccharides. The major surfactant-associated ligand is phosphatidylinositol. However, SP-D can also interact with nucleic acids and components of the extracellular matrix.
SP-D deficient animals show defective clearance and abnormal responses to a variety of viral, bacterial, and fungal pathogens including Influenza A virus, Respiratory Syncytial Virus, Pseudomonas aeruginosa, and Aspergillus fumigatus. SP-D null mice also show perturbations in surfactant lipid homeostasis, defective clearance of nucleic acids and apoptotic cells, abnormal immune responses to microbial antigens, accumulations of activated lymphocytes, and lung remodeling with emphysema.