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The complement system has been thought to originate exclusively in the deuterostomes. Here, we show that the central complement components already existed in the primitive protostome lineage. A functional homolog of vertebrate complement 3, CrC3, has been isolated from a 'living fossil', the horseshoe crab (Carcinoscorpius rotundicauda). CrC3 resembles(More)
The knowledge of how organisms fight infections has largely been built upon the ability of host innate immune molecules to recognize microbial determinants. Although of overwhelming importance, pathogen recognition is but only one of the facets of innate immunity. A primitive yet effective antimicrobial mechanism which operates by depriving microbial(More)
As a structural component of the outer membrane of Gram-negative bacteria, endotoxin, also known as lipopolysaccharide (LPS) exhibits strong immunostimulatory properties, rendering it a pivotal role in the pathogenesis of Gram-negative septicaemia. Our attempt to identify LPS-binding proteins from the hemolymph of the horseshoe crab led to the isolation and(More)
The fifth and the most well-conserved member of the TLR (Toll-like receptor) adaptor, SARM (sterile α- and HEAT/armadillo-motif-containing protein), has been reported to be an important mediator of apoptosis. However, the exact cellular localization of SARM with respect to its role is unclear. In the present study we show that SARM specifically co-localizes(More)
Following acute-phase infection, activated T cells are terminated to achieve immune homeostasis, failure of which results in lymphoproliferative and autoimmune diseases. We report that sterile α- and heat armadillo-motif-containing protein (SARM), the most conserved Toll-like receptors adaptor, is proapoptotic during T-cell immune response. SARM expression(More)
The vitellogenin receptor (VtgR) belongs to the low density lipoprotein receptor (LDLR) gene family. It mediates the uptake of vitellogenin (Vtg) in oocyte development of oviparous animals. In this study, we cloned and characterized two forms of Oreochromis aureus VtgR. Northern analysis showed that VtgR was specifically expressed in ovarian tissues.(More)
For nearly five decades since its discovery, the role of natural IgG, which pre-exists in neonates and uninfected individuals, has remained unclear due to the general perception that natural antibodies lack affinity for pathogens. Here, we show for the first time that natural IgG recognizes a spectrum of bacteria through lectins like ficolin and mannose(More)
The complement system is key to innate immunity and its activation is necessary for the clearance of bacteria and apoptotic cells. However, insufficient or excessive complement activation will lead to immune-related diseases. It is so far unknown how the complement activity is up- or down- regulated and what the associated pathophysiological mechanisms are.(More)
The intrinsic cytotoxicity of cell-free haemoglobin (Hb) has hampered the development of reliable Hb-based blood substitutes for over seven decades. Notably, recent evidence shows that the Hb deploys this cytotoxic attack against invading microbes, albeit, through an unknown mechanism. Here, we unraveled a rapid molecular reprogramming of the Hb(More)
S3 peptide, derived from the Sushi 3 domain of Factor C, which is the lipopolysaccharide (LPS)-sensitive serine protease of the horseshoe crab coagulation cascade, was shown previously to harbor antimicrobial activity against Gram-negative bacteria. However, the mechanism of action remains poorly understood at the molecular level. Here we demonstrate that(More)