Pattern Recognition Proteins Research Articles

Comparative transcriptome analysis reveals potential anti-viral immune pathways of turbot (Scophthalmus maximus) subverted by megalocytivirus RBIV-C1 for immune evasion

Successful viral infection and multiplication chiefly rely on virus subversion mechanisms against host anti-viral immune responses. In this study, in order to reveal the anti-viral immune-related pathways suppressed by megalocytivirus infection, transcriptome analysis was performed on the head-kidney of turbot (Scophthalmus maximus) infected with lethal dose of RBIV-C1 at 3, 6 and 9 days post challenge (dpc). The results showed that, compared to unchallenged groups, 190, 1220, and 3963 DEGs were detected in RBIV-C1 infected groups at 3, 6 and 9 dpc, respectively, of which, DEGs of complement components and pattern recognition proteins were up-regulated at 3 dpc and down-regulated at 6 and 9 dpc, DEGs of cytokines were up-regulated at 6 dpc and down-regulated at 9 dpc. Expression trend analysis revealed that DEGs of profiles 9 and 13 featured decreased expression patterns and were significantly enriched into 10 immune-related pathways, i.e., complement and coagulation cascades, cytokine-cytokine receptor interaction, chemokine signaling pathway, B/T cell receptor signaling pathway, antigen processing and presentation, and so on. Further co-expression network analysis (WGCNA) revealed positive correlated innate immune related pathways at 3 and 6 dpc, and negative correlated innate and adaptive immune related pathways at 9 dpc. This study revealed a set of anti-viral immune genes/pathways that would also be potential targets subverted by RBIV-C1 for immune evasion, which can serve as a valuable resource for future studies on the molecular mechanisms of anti-viral immune defense of turbot and immune escape of megalocytivirus.

Commentary: Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

Commentary: Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

Hemocyte proteome of the Lake Baikal endemic <em>Eulimnogammarus verrucosus</em> (Crustacea: Amphipoda) sheds light on immune-related proteins

Hemocytes are cells circulating in the hemolymph and playing an important role in crustacean immunity. These cells not only function as phagocytes but also express immune compounds to the hemolymph. Here we obtained hemocyte proteome of the endemic amphipod (Amphipoda, Crustacea) Eulimnogammarus verrucosus from Lake Baikal, the first hemocyte proteome of an amphipod, using liquid chromatography/tandem mass spectrometry (LC-MS/MS). A total of 1152 unique proteins were discovered with LC-MS/MS. We discovered both proteins directly involved in the immune response, such as pattern recognition proteins (C-type lectins), and compounds with antimicrobial activity (ctenidin and anti-lipopolysaccharide factor/scygonadin). Moreover, hemocyanins which may act as a phenoloxidase and C-type lectins were among the most diverse protein groups in the hemocyte proteome. The obtained data can be useful for further studies of immune components and mechanisms in Baikal amphipods.

A novel ML protein functions as a pattern recognition protein in antibacterial responses in Eriocheir sinensis

The myeloid differentiation factor 2 (MD-2)-related lipid recognition (ML) domain is present in MD-2, MD-1, GM2-activator protein (GM2A) and Niemann-Pick disease type C2 (NPC2). ML proteins function in antibacterial signal transduction and lipid metabolism in vertebrates, but the mechanism in invertebrates is unknown. In this study, we found that ML proteins were involved in bacterial resistance in Chinese mitten crab (Eriocheir sinensis). One member, EsML3, a soluble, bacterial-induced pattern recognition protein was upregulated in hemocytes following bacterial challenge. Recombinant EsML3 bound to Gram-negative bacteria (Vibrio parahaemolyticus) and Gram-positive bacteria (Staphylococcus aureus) by interaction with peptidoglycan, lipopolysaccharide. EsML3 showed no direct bacteriostatic or bacteriocidal activity. Pre-incubating bacteria with rEsML3 significantly promoted in vivo bacterial clearance. EsML3 also promoted phagocytic activity and plays a role against bacterial infection. In summary, EsML3 mediates cellular immune responses by recognising invasive microorganisms, promoting bacterial clearance and phagocytosis against bacterial infection in crab.

Pattern Recognition Proteins: First Line of Defense Against Coronaviruses.

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

Transcriptomic analysis of the black tiger shrimp (Penaeus monodon) reveals insights into immune development in their early life stages

With the rapid growth in the global demand, the shrimp industry needs integrated approaches for sustainable production. A high-quality shrimp larva is one of the crucial key requirements to maximize shrimp production. Survival and growth rates during larval development are often criteria to evaluate larval quality, however many aspects of gene regulation during shrimp larval development have not yet been identified. To further our understanding of biological processes in their early life, transcriptomic analysis of larval developmental stages (nauplius, zoea, mysis, and postlarva) were determined in the black tiger shrimp, Penaeus monodon using next-generation RNA sequencing. Gene clustering and gene enrichment analyses revealed that most of the transcripts were mainly related to metabolic processes, cell and growth development, and immune system. Interestingly, Spätzle and Toll receptors were found in nauplius stage, providing evidence that Toll pathway was a baseline immune system established in early larval stages. Genes encoding pathogen pattern-recognition proteins (LGBP, PL5-2 and c-type lectin), prophenoloxidase system (PPAE2, PPAF2 and serpin), antimicrobial peptides (crustin and antiviral protein), blood clotting system (hemolymph clottable protein) and heat shock protein (HSP70) were expressed as they developed further, suggesting that these immune defense mechanisms were established in later larval stages.

A C-type lectin with a single CRD from Onychostoma macrolepis mediates immune recognition against bacterial challenge

C-type lectins (CTL) are a large group of pattern-recognition proteins and to play important roles in glycoprotein metabolism, multicellular integration, and immunity. Based on their overall domain structure, they can be classified as different groups that possess different physiological functions. A typical C-type lectin (named as OmLec1) was identified from the fish, Onychostoma macrolepis, an important cultured fish in China. Open reading frame of OmLec1 contains a 570 bp, encoding a protein of 189 amino acids that includes a signal peptide and a single carbohydrate-recognition domain. The phylogenetic analysis showed that OmLec1 could be grouped with C-type lectin from other fish. OmLec1 was expressed in all the tissues in our study, and the expression level was highest in liver. And its relative expression levels were significantly upregulated following infection with Aeromonas hydrophila. The recombinant OmLec1 protein (rOmLec1) could agglutinate some Gram-negative bacteria and Gram-positive bacteria in vitro in the presence of Ca2+, showing a typical Ca2+-dependent carbohydrate-binding protein. Furthermore, rOmLec1 purified from E. coli BL21 (DE3), strongly bound to LPS and PGN, as well as all tested bacteria in a Ca2+-dependent manner. These results indicate that OmLec1 plays a central role in the innate immune response and as a pattern recognition receptor that recognizes diverse pathogens among O. macrolepis.

Early Changes in Crayfish Hemocyte Proteins after Injection with a β-1,3-glucan, Compared to Saline Injected and Naive Animals.

Early changes in hemocyte proteins in freshwater crayfish Pacifastacus leniusculus, in response to an injection with the fungal pattern recognition protein β-1,3-glucan (laminarin) were investigated, as well as changes after saline (vehicle) injection and in naïve animals. Injection of saline resulted in rapid recruitment of granular hemocytes from surrounding tissues, whereas laminarin injection on the other hand induced an initial dramatic drop of hemocytes. At six hours after injection, the hemocyte populations therefore were of different composition. The results show that mature granular hemocytes increase in number after saline injection as indicated by the high abundance of proteins present in granular cell vesicles, such as a vitelline membrane outer layer protein 1 homolog, mannose-binding lectin, masquerade, crustin 1 and serine protease homolog 1. After injection with the β-1,3-glucan, only three proteins were enhanced in expression, in comparison with saline-injected animals and uninjected controls. All of them may be associated with immune responses, such as a new and previously undescribed Kazal proteinase inhibitor. One interesting observation was that the clotting protein was increased dramatically in most of the animals injected with laminarin. The number of significantly affected proteins was very few after a laminarin injection when compared to uninjected and saline-injected crayfish. This finding may demonstrate some problematic issues with gene and protein expression studies from other crustaceans receiving injections with pathogens or pattern recognition proteins. If no uninjected controls are included and no information about hemocyte count (total or differential) is given, expressions data for proteins or mRNAs are very difficult to properly interpret.

Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders.

Toll-like receptors (TLRs), a class of pattern recognition proteins, play an integral role in the modulation of systemic inflammatory responses. Cerebrovascular diseases (CVDs) are a group of pathological conditions that temporarily or permanently affect the brain tissue mostly via the decrease of oxygen and glucose supply. TLRs have a critical role in the activation of inflammatory cascades following hypoxic-ischemic events and subsequently contribute to neuroprotective or detrimental effects of CVD-induced neuroinflammation. The TLR signaling pathway and downstream cascades trigger immune responses via the production and release of various inflammatory mediators. The present review describes the modulatory role of the TLR signaling pathway in the inflammatory responses developed following various CVDs and discusses the potential benefits of the modulation of different TLRs in the improvement of functional outcomes after brain ischemia.

Extracellular signal-regulated kinase 1/2 is required for complement component C1q and fibronectin dependent enhancement of Fc\u03b3- receptor mediated phagocytosis in mouse and human cells

BackgroundC1q is a soluble pattern recognition protein that regulates multiple leukocyte functions, and deficiency in C1q results in autoimmunity. C1q stimulates enhanced phagocytic function through multiple mechanisms including the rapid enhancement of Fcγ receptor (FcγR) -mediated phagocytosis. The molecular mechanism responsible for this rapid enhancement of phagocytic function is unknown. The purpose of this study was to investigate the molecular pathway required for C1q-dependent enhanced phagocytosis.ResultsLeukocyte associated immunoglobulin like receptor-1 (LAIR-1) is a receptor that mediates C1q-dependent activation of leukocytes; however, using LAIR-1 deficient mouse bone marrow derived macrophages (BMDM), we demonstrated that LAIR-1 was not required for C1q-dependent enhanced FcγR-mediated phagocytosis. A phospho-kinase array identified extracellular signal-regulated kinase (ERK) 1/2 as dysregulated following activation with C1q. Validation of the array in BMDM and the human monocyte cell line THP-1 demonstrated a decrease in basal ERK1/2 phosphorylation in C1q-stimulated cells compared to control cells. However, subsequent stimulation with immune complexes stimulated rapid upregulation of phosphorylation. The extracellular matrix protein fibronectin regulates enhanced phagocytic activity in macrophages similar to C1q, and both C1q and fibronectin-dependent enhanced phagocytosis required ERK1/2 since both were blocked by pharmacologic inhibition of ERK1/2. Furthermore, diminished C1q-dependent ERK1/2 phosphorylation was sustained after four-hour treatment with lipopolysaccharide and correlated with a significant reduction in TNFα production.ConclusionsThese data demonstrate that C1q and fibronectin utilize a similar ERK1/2-dependent mechanism for enhanced phagocytosis, which should lead to development of novel approaches to modulate C1q-dependent regulation of macrophage activation, inflammation and autoimmunity.

Transformation of glycerate kinase (GLYK) into Metarhizium acridum increases virulence to locust.

Improvements in the virulence of the fungal pathogen Metarhizium acridum can crucially promote its efficacy to control locusts and grasshoppers. The polysaccharide components of the cell wall remarkably contribute to fungal virulence. Here we found that M. acridum lacked the gene families of glycerate-3-kinase (GLYK) as the synthesis enzymes of saccharides. We then generated mutants by introducing the GLYK gene from the host-generalist M. robertsii into the host-specialist M. acridum. Consequently, compared with the wild-type strain, the mutant strain (Ma::MrGLYK) increased the level of phospho-6-fructose in mycelia, the length and density of the mannan fibril layer on the cell wall. The mutant strains increased the mannan fibril in the cell wall and resistance to heat stress. Further transcriptome analysis showed that compared with the wild-type strain, topical infection of Ma::MrGLYK strain induced higher expression of genes such as pattern-recognition proteins, serine protease, and CYP450s in locusts, while reduced the expression of antimicrobial peptide and phenoloxidase activity. Moreover, topical infection and injection of Ma::MrGLYK significantly increased the mortality and shortened the lifespan of locusts compared with wild-type M. acridum. Our study highlighted the application potential of the novel genetically modified fungal mutant of the host-specialist M. acridum as a biocontrol agent against locust plagues. © 2020 Society of Chemical Industry.

Scavenger receptor B8 improves survivability by mediating innate immunity in silkworm, Bombyx mori

Scavenger receptor class B (SR-B) is an extracellular transmembrane glycoprotein that plays a vital role in innate immunity. Although SR-Bs have been widely studied in vertebrates, their functions remained to elucidate in insects. Here, we identified and characterized a scavenger receptor class B member from the silkworm, Bombyx mori (designated as BmSCRB8). BmSCRB8 is broadly expressed in various immune tissues/organs, including fat body, gut, and hemocyte. Its expression is dramatically enhanced after challenge with different types of bacteria or pathogen-associated molecular patterns (PAMPs). The recombinant BmSCRB8 protein can detect different types of bacteria by directly binding to PAMPs and significantly improve the bacterial clearance in vivo. After knockdown of BmSCRB8, the pathogenic bacterial clearance was strongly impaired, and several AMP genes were down-regulated following E. coli challenge. Moreover, pathogenic bacteria's treatment following the depletion of BmSCRB8 remarkably decreased silkworm larvae's survival rate. Taken together, these results demonstrate that BmSCRB8 acts as a pattern recognition protein and plays an essential role in silkworm innate immunity by enhancing bacterial clearance and contributing to the production of AMPs in vivo.

Transcriptomic analysis and expression of C-type lectins in response to Vibrio parahaemolyticus challenge in Scapharca subcrenata

Little information is available on innate immune defense mechanisms of Scapharca subcrenata. C-type lectins (CTLs) are not only pattern recognition proteins that can bind pathogen-associated molecular patterns, but also crucial maternally-derived immune factors in mollusc egg. In this study, the comparative transcriptome analysis of Vibrio parahaemolyticus-infected and untreated hepatopancreas were performed to identify the key genes involved in maternal transfer of immunity. A total of 3514 and 9327 differentially expressed genes (DEGs) were identified at 6 and 48 h post challenge compared to control groups. Gene Ontology and Cluster of Orthologous Groups analysis showed that most DEGs were classified under regulation of signal transduction, regulation of the metabolic process of carbohydrates and secondary metabolites, while the processes of posttranscriptional modification and protein translation were inhibited manifestly. The DEGs were most enriched in pathways related to lysosome, phagosome and EMC-receptor interaction. Among the DEGs, 191 maternal immune-related genes that could provide developing embryos a better protection against pathogen infection were identified according to previous studies. Additionally, five CTLs (designated as SsCTL1-5) identified from the DEGs were cloned, and their expression patterns in different tissues and post immune stimulation were analyzed. These findings would be beneficial for understanding the innate immune defense mechanisms of S. subcrenata.

-Omic Analysis of the Sepia officinalis White Body: New Insights into Multifunctionality and Haematopoiesis Regulation

Cephalopods, like other protostomes, lack an adaptive immune system and only rely on an innate immune system. The main immune cells are haemocytes (Hcts), which are able to respond to pathogens and external attacks. First reports based on morphological observations revealed that the white body (WB) located in the optic sinuses of cuttlefish was the origin of Hcts. Combining transcriptomic and proteomic analyses, we identified several factors known to be involved in haematopoiesis in vertebrate species in cuttlefish WB. Among these factors, members of the JAK-STAT signaling pathway were identified, some of them for the first time in a molluscan transcriptome and proteome. Immune factors, such as members of the Toll/NF-κB signaling pathway, pattern recognition proteins and receptors, and members of the oxidative stress responses, were also identified, and support an immune role of the WB. Both transcriptome and proteome analyses revealed that the WB harbors an intense metabolism concurrent with the haematopoietic function. Finally, a comparative analysis of the WB and Hct proteomes revealed many proteins in common, confirming previous morphological studies on the origin of Hcts in cuttlefish. This molecular work demonstrates that the WB is multifunctional and provides bases for haematopoiesis regulation in cuttlefish.

Surfactant Protein D Recognizes Multiple Fungal Ligands: A Key Step to Initiate and Intensify the Anti-fungal Host Defense.

With limited therapeutic options and associated severe adverse effects, fungal infections are a serious threat to human health. Innate immune response mediated by pattern recognition proteins is integral to host defense against fungi. A soluble pattern recognition protein, Surfactant protein D (SP-D), plays an important role in immune surveillance to detect and eliminate human pathogens. SP-D exerts its immunomodulatory activity via direct interaction with several receptors on the epithelial cells lining the mucosal tracts, as well as on innate and adaptive immune cells. Being a C-type lectin, SP-D shows calcium- and sugar-dependent interactions with several glycosylated ligands present on fungal cell walls. The interactome includes cell wall polysaccharides such as 1,3-β-D-glucan, 1,6-β-D-glucan, Galactosaminogalactan Galactomannan, Glucuronoxylomannan, Mannoprotein 1, and glycosylated proteins such as gp45, gp55, major surface glycoprotein complex (gpA). Recently, binding of a recombinant fragment of human SP-D to melanin on the dormant conidia of Aspergillus fumigatus was demonstrated that was not inhibited by sugars, suggesting a likely protein-protein interaction. Interactions of the ligands on the fungal spores with the oligomeric forms of full-length SP-D resulted in formation of spore-aggregates, increased uptake by phagocytes and rapid clearance besides a direct fungicidal effect against C. albicans. Exogenous administration of SP-D showed significant therapeutic potential in murine models of allergic and invasive mycoses. Altered susceptibility of SP-D gene-deficient mice to various fungal infections emphasized relevance of SP-D as an important sentinel of anti-fungal immunity. Levels of SP-D in the serum or lung lavage were significantly altered in the murine models and patients of fungal infections and allergies. Here, we review the cell wall ligands of clinically relevant fungal pathogens and allergens that are recognized by SP-D and their impact on the host defense. Elucidation of the molecular interactions between innate immune humoral such as SP-D and fungal pathogens would facilitate the development of novel therapeutic interventions.

A typical C-type lectin, perlucin-like protein, is involved in the innate immune defense of whiteleg shrimp Litopenaeus vannamei

C-type lectins are a large group of the pattern-recognition proteins, and have been reported to be involved in invertebrate innate immunity, such as cell adhesion, bacterial clearance, phagocytosis, prophenoloxidase activation and encapsulation. Here, a perlucin-like protein (PLP), a typical C-type lectin, was identified from the cDNA library of the shrimp, Litopenaeus vannamei. LvPLP contains a 540 bp open reading frame, encoding a protein of 179 amino acids that includes a single carbohydrate-recognition domain. Phylogenetic analysis showed that LvPLP was clustered into a single group together with other perlucins from molluscs. Quantitative real-time PCR revealed that LvPLP was expressed mainly in the hemocytes, hemolymph, heart and gills. The transcription of LvPLP was significantly induced at 9 h by both Gram− bacteria Vibrio parahaemolyticus and Vibrio anguillarum. Meanwhile, recombinant LvPLP (rLvPLP) bound directly to lipopolysaccharide and peptidoglycan with different affinity. rLvPLP showed a strong ability to bind to Gram+ (Staphylococcus aureus and Bacillus subtilis) and Gram− bacteria (V. parahaemolyticus and V. anguillarum), and could induce agglutination of V. parahaemolyticus and V. anguillarum, but not S. aureus and B. subtilis in the presence Ca2+. Further study showed that when LvPLP was knocked down by RNAi, three phagocytosis-related genes (peroxinectin, mas-like protein and dynamin) and four antimicrobial peptide (AMP) genes (crustin, ALF1, ALF2 and ALF3) were significantly decreased. Altogether, these results demonstrated that LvPLP played a vital role in L. vannamei immune response towards bacterial challenge by binding and agglutinating bacteria and influencing phagocytosis and AMP expression.

The N-terminal peptide generated after activation of prophenoloxidase affects crayfish hematopoiesis

The circulating hemocytes of invertebrates are important mediators of immunity, and hemocyte homeostasis is of high importance for survival and health of crustaceans. The prophenoloxidase (proPO)-activating system is one of the most essential immune reactions, which can be activated by pattern recognition proteins from microorganisms. Activation of proPO by the proPO activating enzyme generates an N-terminal peptide, with cleavage site after Arg176, as well as the active enzyme phenoloxidase, which is the key enzyme for melanization. In the present study we demonstrate a role for the N-terminal proPO-peptide in hematopoiesis. Injection of this proPO-peptide increased the number of circulating hemocytes and especially granular hemocytes. We also show that the reactive oxygen species (ROS) production in the anterior proliferative center was enhanced after proPO peptide injection, which is a prerequisite for rapid hemocyte release from the hematopoietic tissue. Moreover, this peptide had an effect on ROS production in in vitro cultured hematopoietic cells and induced spreading of these cells within 72 h. Taken together, our findings show a role of the N-terminal proPO peptide in stimulation of hematopoiesis in crayfish, Pacifastacus leniusculus.

Probiotic, Bacillus subtilis E20 alters the immunity of white shrimp, Litopenaeus vannamei via glutamine metabolism and hexosamine biosynthetic pathway

The purpose of this study was to profile the mechanisms of action of probiotic, Bacillus subtilis E20 in activating the immunity of white shrimp, Litopenaeus vannamei. Two groups of shrimp were studied. One group was fed a control diet without probiotic supplementation and the other was fed a probiotic-containing diet at a level of 109 cfu kg diet−1. After the 8-week feeding regimen, the metabolite composition in the hepatopancreas of shrimp were investigated using 1H nuclear magnetic resonance (1H NMR) based metabolomic analysis. Results from the 1H NMR analysis revealed that 16 hepatopancreatic metabolites were matched and identified among groups, of which 2 metabolites, creatinine and glutamine were significantly higher in probiotic group than in the control group. This result was confirmed by the reverse-phase high-performance liquid chromatography (RP-HPLC) and spectrophotometric analysis. Transcriptome analysis indicated the expressions of 10 genes associated with antioxidant enzymes, pattern recognition proteins and antimicrobial molecules, more active expression in the shrimp fed a diet supplemented with probiotic as compared to that of shrimp in control. In addition, the expressions of 4 genes involved with hexosamine biosynthesis pathway (HBP) and UDP-N-acetylglucosamine-peptide N-acetylglucosaminyltransferase for protein O-glycosylation were also higher in hepatopancreas of probiotic-treated shrimp than in shrimp fed a control diet. Western blot and enzyme-linked immunosorbent assay showed that heat shock factor 1, heat shock protein 70, and protein O-glycosylation in hepatopancreas were higher in probiotic group than the control group. These findings suggest that probiotic, B. subtilis E20 promotes the digestibility of glutamine in the diet, and that the increased glutamine in shrimp can be used as fuel for immune cells or may be used to regulate immune molecule expressions and protein O-glycosylation via the HBP to increase protein O-glycosylation, thereby improving the health of shrimp.

Lipoprotein receptor signalling in atherosclerosis.

The founding member of the lipoprotein receptor family, low-density lipoprotein receptor (LDLR) plays a major role in the atherogenesis through the receptor-mediated endocytosis of LDL particles and regulation of cholesterol homeostasis. Since the discovery of the LDLR, many other structurally and functionally related receptors have been identified, which include low-density lipoprotein receptor-related protein (LRP)1, LRP5, LRP6, very low-density lipoprotein receptor, and apolipoprotein E receptor 2. The scavenger receptor family members, on the other hand, constitute a family of pattern recognition proteins that are structurally diverse and recognize a wide array of ligands, including oxidized LDL. Among these are cluster of differentiation 36, scavenger receptor class B type I and lectin-like oxidized low-density lipoprotein receptor-1. In addition to the initially assigned role as a mediator of the uptake of macromolecules into the cell, a large number of studies in cultured cells and in in vivo animal models have revealed that these lipoprotein receptors participate in signal transduction to modulate cellular functions. This review highlights the signalling pathways by which these receptors influence the process of atherosclerosis development, focusing on their roles in the vascular cells, such as macrophages, endothelial cells, smooth muscle cells, and platelets. Human genetics of the receptors is also discussed to further provide the relevance to cardiovascular disease risks in humans. Further knowledge of the vascular biology of the lipoprotein receptors and their ligands will potentially enhance our ability to harness the mechanism to develop novel prophylactic and therapeutic strategies against cardiovascular diseases.

A novel hexamerin with an unexpected contribution to the prophenoloxidase activation system of the Chinese oak silkworm, Antheraea pernyi.

Hexamerin was originally identified as a storage protein but later confirmed to be involved in many physiological processes. In the present study, we cloned and characterized a novel hexamerin complementary DNA sequence from the Chinese oak silkworm, Antheraea pernyi (Ap-hexamerin), which shows high homology with reported insect methionine-rich hexamerins. The tissue distribution and time course of expression demonstrated that Ap-hexamerin was predominantly synthesized in the fat body and the expression level was significantly increased in response to the microbial challenge, suggesting the relevance of Ap-hexamerin to immune responses. In further immune functional studies, Ap-hexamerin was confirmed to take part in the upregulation of prophenoloxidase (PPO) activation in A. pernyi haemolymph triggered by pathogen-associated molecular patterns (PAMPs). Additional molecular interaction analysis revealed that Ap-hexamerin is capable of binding the PAMPs used in the phenoloxidase assay, suggesting hexamerin in A. pernyi may positively regulate haemolymph PPO activation, acting as a pattern recognition protein.