Complement proteins C1q and MBL are pattern recognition molecules that signal immediate and long-term protective immune functions.
C1q and mannose binding lectin, members of the "defense collagen" family, are pattern recognition molecules that can trigger rapid enhanced phagocytosis resulting in efficient containment of pathogens or clearance of cellular debris, apoptotic cells and immune complexes. In addition, interaction of C1q and mannose binding lectin with the phagocyte alters subsequent phagocyte cytokine synthesis, and thus may have important implications in directing acute inflammation as well as long-term protective immunity. The importance of the role of defense collagens in phagocytosis of apoptotic cells is highlighted by studies in vivo of mice deficient in C1q, pulmonary surfactant D and mannose binding lectin in which there is delayed clearance of apoptotic cells. Indeed, deficiency of C1q is a risk factor for the development of autoimmunity in both humans and mice, consistent with the hypothesis that inefficient clearance of apoptotic cells results in release of autoantigens and contributes to the pathology associated with autoimmune diseases such as systemic lupus erythematosus. Further understanding of the importance of C1q and mannose binding lectin in the clearance of apoptotic cells and regulation of cytokine synthesis and identification of the receptors implicated in mediating these processes should provide novel targets for therapeutic intervention in the control and manipulation of the immune response in terms of both host defense against infectious disease and tissue repair and remodeling.
Bohlson
Suzanne S
SS
Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, CA 92697, USA.
Fraser
Deborah A
DA
Tenner
Andrea J
AJ
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D037282:Calreticulin / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D015922:Complement C1q / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000502:physiology*; D010587:Phagocytosis; D051192:Receptors, Pattern Recognition / Q000502:physiology*; D015398:Signal Transduction
D015703:Antigens, CD; D037282:Calreticulin; D016207:Cytokines; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D037601:Mannose-Binding Lectin; D051192:Receptors, Pattern Recognition; D015922:Complement C1q; D003094:Collagen