The lectin-complement pathway--its role in innate immunity and evolution.
Innate immunity was formerly thought to be a non-specific immune response characterized by phagocytosis. However, innate immunity has considerable specificity and is capable of discriminating between pathogens and self. Recognition of pathogens is mediated by a set of pattern recognition receptors, which recognize conserved pathogen-associated molecular patterns (PAMPs) shared by broad classes of microorganisms, thereby successfully defending invertebrates and vertebrates against infection. Lectins, carbohydrate-binding proteins, play an important role in innate immunity by recognizing a wide range of pathogens. Mannose-binding lectin (MBL) and ficolin are lectins composed of a lectin domain attached to collagenous region. However, they use a different lectin domain: a carbohydrate recognition domain (CRD) is responsible for MBL and a fibrinogen-like domain for ficolin. These two collagenous lectins are pattern recognition receptors, and upon recognition of the infectious agent, they trigger the activation of the lectin-complement pathway through attached serine proteases, MBL-associated serine proteases (MASPs). A similar lectin-based complement system, consisting of the lectin-protease complex and C3, is present in ascidians, our closest invertebrate relatives, and functions in an opsonic manner. We isolated several lectins homologous to MBLs and ficolins and several MASPs in invertebrates and lower vertebrates, and herein we discuss the molecular evolution of these molecules. Based on these findings, it seems likely that the complement system played a pivotal role in innate immunity before the evolution of an acquired immune system in jawed vertebrates.
Fujita
Teizo
T
Department of Biochemistry, Fukushima Medical University, Fukushima, Japan. tfujita@fmu.ac.jp
Matsushita
Misao
M
Endo
Yuichi
Y
D000818:Animals; D005075:Biological Evolution; D003167:Complement Activation; D037582:Complement Pathway, Mannose-Binding Lectin; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000737:chemistry / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000737:chemistry; D008954:Models, Biological; D010802:Phylogeny; D015398:Signal Transduction; D000097604:Ficolins
D003165:Complement System Proteins; D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins