Sadaaki Iwanaga: discovery of the lipopolysaccharide- and -1,3-D-glucan-mediated proteolytic cascade and unique proteins in invertebrate immunity

Horseshoe crab hemolymph contains a single type of cells, granular hemocytes, which are extremely sensitive to bacterial lipopolysaccharides (LPS) and lead to hemolymph coagulation.Sadaaki Iwanaga isolated protease zymogens from the hemocytes and reconstituted LPS and β-1,3-D-glucans-mediated hemolymph coagulation.This led to the first discovery of a proteolytic cascade triggered by pathogen-associated molecular patterns, an important milestone for studies on invertebrate innate immunity.Moreover, he separated components derived from hemocyte granules and hemolymph plasma, and consequently identified unique defense molecules, such as lectins, serpins, cystatins, antimicrobial substances, and substrates for transglutaminase.Through steady and persistent studies on the horseshoe crab host defense system, he made great progress in the field.Now we know that LPS-induced hemocyte exocytosis leads not only to coagulation but also activates a sophisticated immune response network that coordinately induces pathogen recognition, elimination, and wound healing.