[Recent advances in innate immune host defense--hose defense lectins and endotoxin receptors]

Accumulating evidence has revealed that CD14 and Toll-like receptors (TLRs) function as pattern recognition receptors for broad ranges of pathogens. The structural characteristics of these proteins is that they possess leucine-rich repeats, which appear to be involved in protein-protein interaction. We have shown that the extracellular TLR2 domain directly binds to peptidoglycan (PGN) which is abundant in the cell wall of Gram-positive bacteria and that the N-terminal region of TLR2 is critical for the recognition of PGN. Surfactant proteins A and D (pulmonary collectins) function as host defense lectins and play important roles in innate immunity in the lung-Collectins including SP-A, SP-D and mannose-binding proteins can bind CD14. We have demonstrated that SP-A modulates the cellular response to smooth and rough lipopolysaccharides (LPS) by interaction with CD14. In addition, this protein has been revealed to function as a negative regulator against PGN-induced TNF-alpha secretion from macrophages through direct interaction with TLR2. We propose that SP-A modulates inflammatory responses against the bacterial components by interaction with pattern-recognition receptors.