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Effect of PHA and LPS on the Activity of Nonspecific Cytotoxic Cells and Macrophages of Rainbow Trout (Oncorhynchus mykiss) Gayana
Gómez,Leonardo A; Cortés,Raúl; Smith,Carlos T.
This work studied the effect of the lectin phytohaemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) on the activity of nonspecific cytotoxic cells (NCCs) and macrophages of peripheral blood in the rainbow trout. NCCs are cells of the innate immunity, homologues to Natural Killer (NK) cells of mammals, capable of eliminating cells infected with intracellular pathogens and also tumoral cells. Their lytic activity is mediated by the perforin/granzyme system and the Fas receptor-Fas ligand (FasR-FasL) system. Activity of NCCs was evaluated by their capacity to lyse HL-60 tumor cells. On the other hand, macrophages eliminate microorganisms by several mechanisms, including the production of reactive oxygen species (ROS) and nitric oxide (NO). Results...
Tipo: Journal article Palavras-chave: Interleukins; Innate immunity; FasR-FasL; Lectins; Leukocytes.
Ano: 2013 URL: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-65382013000100007
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Molecular cloning and mRNA expression of the peptidoglycan recognition protein gene HcPGRP1 and its isoform HcPGRP1a from the freshwater mussel Hyriopsis cumingi Genet. Mol. Biol.
Tao,Ye; Yang,Zi-yan; Zhang,Xin; Wu,Hong-juan.
Peptidoglycan recognition proteins (PGRPs) are innate immune molecules that have been structurally conserved throughout evolution in invertebrates and vertebrates. In this study, peptidoglycan recognition protein HcPGRP1 and its isoform HcPGRP1a were identified in the freshwater mussel Hyriopsis cumingii. The full-length cDNAs of HcPGRP1 (973 bp) and HcPGRP1a (537 bp) encoded polypeptides with 218 and 151 amino acids, respectively. Sequence analysis showed that HcPGRP1 had one C-terminal PGRP domain that was conserved throughout evolution. Phylogenetic analysis showed that HcPGRP1 clustered closely with EsPGRP4 of Euprymna scolopes. Real-time PCR showed that the mRNA transcripts of HcPGRP1 and HcPGRP1a were constitutively expressed in various tissues, with...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Expression pattern; Gene cloning; Hyriopsis cumingi; Innate immunity; Peptidoglycan recognition protein.
Ano: 2014 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572014000400006
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Up-regulation of RIP1 and IPS-1 in chronic HBV infected patients Genet. Mol. Biol.
Safari-Arababadi,Minoo; Modarressi,Mohammad Hossein; Arababadi,Mohammad Kazemi.
Abstract IPS-1 and RIP1 are the main downstream molecules of RIG1 and MDA5, as intracytoplasmic receptors, which are the main receptors involved in recognition of internal and external viral double-stranded RNA. In this project, mRNA levels of IPS-1 and RIP1 were investigated in the peripheral blood immune cells of chronic hepatitis B (CHB) patients. IPS-1 and RIP1 mRNA levels were measured in 60 CHB patients and 120 healthy subjects, using RT-qPCR technique. A significant increase in expression levels of IPS-1 and RIP1 was found in patients when compared to healthy individuals. There was no correlation between IPS-1 and RIP1expression levels with the serum levels of hepatitis B e-Antigen (HBeAg) and liver enzymes in patients. Based on the results, it...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Innate immunity; Hepatitis B; RIP1; IPS-1.
Ano: 2019 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572019000300337
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Expression, tissue localization and synergy of antimicrobial peptides and proteins in the immune response of the oyster Crassostrea gigas ArchiMer
Schmitt, Paulina; De Lorgeril, Julien; Gueguen, Yannick; Destoumieux-garzon, Delphine; Bachere, Evelyne.
Diverse families of antimicrobial peptides and proteins have been described in oysters. We investigated here how antimicrobials are involved in the immune response against a pathogenic strain of Vibrio splendidus. Oyster antimicrobials were shown to display a wide variety of expression profiles in hemocyte populations and tissues. Oyster defensins are constitutively expressed in specific tissues such as mantle (Cg-Defm) or hemocytes (Cg-Defhs), while Cg-BPI is inducible and Cg-Prp appears down-regulated in hemocytes upon infection. The migratory behavior of hemocytes that express the different antimicrobials was found to be involved in the oyster response to a pathogenic Vibrio infection. Indeed, it contributes to colocalize several antimicrobials that...
Tipo: Text Palavras-chave: Pacific oyster; Bivalve mollusk; Innate immunity; Bactericidal/permeability-increasing protein; Proline-rich peptide; Defensin; Vibrio.
Ano: 2012 URL: http://archimer.ifremer.fr/doc/00093/20382/18267.pdf
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Cecropins as a marker of Spodoptera frugiperda immunosuppression during entomopathogenic bacterial challenge ArchiMer
Duvic, B.; Jouan, V.; Essa, N.; Girard, P-a; Pages, S.; Khattar, Z. Abi; Volkoff, N-a; Givaudan, A.; Destoumieux-garzon, Delphine; Escoubas, Jean-michel.
An antimicrobial peptide (AMP) of the cecropin family was isolated by HPLC from plasma of the insect pest, Spodoptera frugiperda. Its molecular mass is 3910.9 Da as determined by mass spectrometry. Thanks to the EST database Spodobase, we were able to describe 13 cDNAs encoding six different cecropins which belong to the sub-families CecA, CecB, CecC and CecD. The purified peptide identified as CecB1 was chemically synthesized (syCecB1). It was shown to be active against Gram-positive and Gram-negative bacteria as well as fungi. Two closely related entomopathogenic bacteria, Xenorhabdus nematophila F1 and Xenorhabdus mauleonii VC01(T) showed different susceptibility to syCecB1. Indeed, X. nematophila was sensitive to syCecB1 whereas X. mauleonii had a...
Tipo: Text Palavras-chave: Humoral immunity; Innate immunity; Immunosuppression; Lepidopteran; Invertebrate.
Ano: 2012 URL: http://archimer.ifremer.fr/doc/00086/19728/17485.pdf
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First evidence for a Vibrio strain pathogenic to Mytilus edulis altering hemocyte immune capacities ArchiMer
Ben Cheikh, Yosra; Travers, Marie-agnes; Morga, Benjamin; Godfrin, Yoann; Rioult, Damien; Le Foll, Franck.
Bacterial isolates were obtained from mortality events affecting Mytilus edulis and reported by professionals in 2010-2013 or from mussel microflora. Experimental infections allowed the selection of two isolates affiliated to V. splendidus/V. hemicentroti type strains: a virulent 10/068 1T1 (76,6% and 90% mortalities in 24h and 96h) and an innocuous 12/056 M24T1 (0% and 23,3% in 24h and 96h). These two strains were GFP-tagged and validated for their growth characteristics and virulence as genuine models for exposure. Then, host cellular immune responses to the microbial invaders were assessed. In the presence of the virulent strain, hemocyte motility was instantaneously enhanced but markedly slowed down after 2h exposure. By contrast, hemocyte velocity...
Tipo: Text Palavras-chave: Innate immunity; Molluscs; Cell-mediated immune response; Bacterial infections; Green fluorescent protein.
Ano: 2016 URL: http://archimer.ifremer.fr/doc/00302/41336/40522.pdf
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Out of the deep-sea into a land-based aquarium environment: Investigating innate immunity in the hydrothermal vent mussel Bathymodiolus azoricus ArchiMer
Bettencourt, Raul; Costa, Valentina; Laranjo, Mario; Rosa, Domitilia; Pires, Luis; Colaco, Ana; Sarradin, Pierre Marie; Lopes, Humberto; Sarrazin, Marie Josée; Santos, Ricardo Serrao.
Deep-sea hydrothermal vents are considered as some of the most adverse environments in the world, yet the animals dwelling around the vent sites exhibit high productivity and therefore must cope with unusual levels of heavy metals, pH, temperature, CO2 and sulfide, in addition to environmental microbes. In an attempt to understand the physiological reactions of animals normally set to endure extreme conditions we investigated molecular indicators of acclimation processes during which the mussel Bathymodiolus azoricus was maintained over long periods of time under without methane and/or sulfide supplementation, vent mussels seem to endure well aquarium conditions. The presence and induction of a Rel Homology Domain containing gene was investigated along...
Tipo: Text Palavras-chave: Bathymodiolus azoricus; Innate immunity; Gene expression; IPOCAMP; Physiological adaptation; Hydrothermal vent.
Ano: 2010 URL: http://archimer.ifremer.fr/doc/00019/13042/10154.pdf
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BgTEP: An Antiprotease Involved in Innate Immune Sensing in Biomphalaria glabrata ArchiMer
Portet, Anais; Galinier, Richard; Pinaud, Silvain; Portela, Julien; Nowacki, Fanny; Gourbal, Benjamin; Duval, David.
Insect thioester-containing protein (iTEP) is the most recently defined group among the thioester-containing protein (TEP) superfamily. TEPs are key components of the immune system, and iTEPs from flies and mosquitoes were shown to be major immune weapons. Initially characterized from insects, TEP genes homologous to iTEP were further described from several other invertebrates including arthropods, cniderians, and mollusks albeit with few functional characterizations. In the freshwater snail Biomphalaria glabrata, a vector of the schistosomiasis disease, the presence of a TEP protein (BgTEP) was previously described in a well-defined immune complex involving snail lectins (fibrinogen-related proteins) and schistosome parasite mucins (SmPoMuc). To...
Tipo: Text Palavras-chave: Thioester-containing protein; Complement-like protein; Biomphalaria glabrata; Interaction host/pathogens; Innate immunity.
Ano: 2018 URL: https://archimer.ifremer.fr/doc/00444/55548/71780.tif
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Differential distribution and defence involvement of antimicrobial peptides in mussel ArchiMer
Mitta, Guillaume; Vandenbulcke, Franck; Noel, Thierry; Romestand, Bernard; Beauvillain, Jean Claude; Salzet, Michel; Roch, Philippe.
In previous papers, we characterised 3 types of 4-kDa, cysteine-rich, cationic antimicrobial peptides: MGDs (for Mytilus galloprovincialis defensins), mytilins and myticins, which are abundant in the mussel hemocytes. In the present work, me revealed a differential distribution of the cells expressing the different genes. In addition, using confocal and electron microscopy, we confirmed that defensins and mytilins were partially located in different sub-types of circulating hemocytes although the peptides can be located in the same cell, and even in the same granule. We also demonstrated that mytilins exert their microbicidal effect within the cells through the process of phagosome-mytilin granule fusion leading to the co-location of ingested bacteria and...
Tipo: Text Palavras-chave: Innate immunity; Hemocyte; Mussel; Myticin; Mytilin; Defensin; Antimicrobial.
Ano: 2000 URL: http://archimer.ifremer.fr/doc/2000/publication-413.pdf
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Oyster hemocytes express a proline-rich peptide displaying synergistic antimicrobial activity with a defensin ArchiMer
Gueguen, Yannick; Romestand, Bernard; Fievet, Julie; Schmitt, Paulina; Destoumieux Garzon, Delphine; Franck, Vandenbulcke; Philippe, Bulet; Bachere, Evelyne.
A cDNA sequence that encodes a 61-amino acid polypeptide precursor with homologies to proline-rich antimicrobial peptides (AMPs) was identified in the oyster Crassostrea gigas. After release of a hydrophobic signal peptide. the resulting 37-amino acid peptide, Cg-Prp, is composed of an acidic region and a cationic proline-rich region. To evaluate the biological properties of Cg-Prp, multiple proline-rich peptides corresponding to putative processing of the full-length Cg-Prp were synthesized. A limited antimicrobial activity was observed for two of them, which also showed strong synergistic antimicrobial activity with Cg-Def, a defensin from C gigas. To our knowledge, this is the first evidence of synergy between a defensin and another AMP in an...
Tipo: Text Palavras-chave: Antimicrobial peptide; Mollusk; Synergy; Invertebrate; Innate immunity; Pacific oyster.
Ano: 2009 URL: http://archimer.ifremer.fr/doc/2009/publication-6232.pdf
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Infection dynamics of a V. splendidus strain pathogenic to Mytilus edulis : In vivo and in vitro interactions with hemocytes ArchiMer
Ben Cheikh, Yosra; Travers, Marie-agnes; Le Foll, Frank.
The pathogenic strain V. splendidus 10/068 1T1 has previously been reported for its virulence to the blue mussel and for its capacity to alter immune responses. In this study, we expanded the knowledge on hemocyte-pathogen interactions by using in vitro and in vivo assays. V. splendidus 10/068 1T1 severely inhibited cell adhesion and acidic vacuole formation unlike the innocuous phylogenetically related V. splendidus 12/056 M24T1 which had no effect on these cell functions. Furthermore, the virulent bacteria decreased hemocyte viability (59% of viability after 24 h). Infection dynamics were explored by using a model based on water tank cohabitation with septic mussels infected by GFP-tagged V. splendidus 10/068 1T1. Experimental infections were...
Tipo: Text Palavras-chave: Innate immunity; Bivalves; Vibrio; Infection; Experimental model; Hemocyte.
Ano: 2017 URL: http://archimer.ifremer.fr/doc/00400/51136/53772.pdf
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Resistance to Antimicrobial Peptides in Vibrios ArchiMer
Destoumieux-garzón, Delphine; Duperthuy, Marylise; Vanhove, Audrey; Schmitt, Paulina; Wai, Sun.
Vibrios are associated with a broad diversity of hosts that produce antimicrobial peptides (AMPs) as part of their defense against microbial infections. In particular, vibrios colonize epithelia, which function as protective barriers and express AMPs as a first line of chemical defense against pathogens. Recent studies have shown they can also colonize phagocytes, key components of the animal immune system. Phagocytes infiltrate infected tissues and use AMPs to kill the phagocytosed microorganisms intracellularly, or deliver their antimicrobial content extracellularly to circumvent tissue infection. We review here the mechanisms by which vibrios have evolved the capacity to evade or resist the potent antimicrobial defenses of the immune cells or tissues...
Tipo: Text Palavras-chave: Vibrio; Lipopolysaccharide; Outer membrane vesicle; Membrane transporter; Innate immunity; Defensin; Cathelicidin; Bactericidal/permeability-increasing protein.
Ano: 2014 URL: http://archimer.ifremer.fr/doc/00276/38767/37308.pdf
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A Sustained Immune Response Supports Long-Term Antiviral Immune Priming in the Pacific Oyster, Crassostrea gigas ArchiMer
Lafont, Maxime; Vergnes, Agnes; Vidal-dupiol, Jeremie; De Lorgeril, Julien; Gueguen, Yannick; Haffner, Philippe; Petton, Bruno; Chaparro, Cristian; Barrachina, Celia; Destoumieux-garzon, Delphine; Mitta, Guillaume; Gourbal, Benjamin; Montagnani, Caroline.
Over the last decade, innate immune priming has been evidenced in many invertebrate phyla. If mechanistic models have been proposed, molecular studies aiming to substantiate these models have remained scarce. We reveal here the transcriptional signature associated with immune priming in the oyster Crassostrea gigas. Oysters were fully protected against Ostreid herpesvirus 1 (OsHV-1), a major oyster pathogen, after priming with poly(I·C), which mimics viral double-stranded RNA. Global analysis through RNA sequencing of oyster and viral genes after immune priming and viral infection revealed that poly(I·C) induces a strong antiviral response that impairs OsHV-1 replication. Protection is based on a sustained upregulation of immune genes, notably genes...
Tipo: Text Palavras-chave: Innate immunity; Priming; OsHV-1; Antiviral response; Immune memory; Oyster; POMS; Poly(I·C); Interferon; Transcriptomic.
Ano: 2020 URL: https://archimer.ifremer.fr/doc/00614/72580/71541.pdf
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Use of OmpU porins for attachment and invasion of Crassostrea gigas immune cells by the oyster pathogen Vibrio splendidus ArchiMer
Duperthuy, Marylise; Schmitt, Paulina; Garzon, Edwin; Caro, Audrey; Rosa, Rafael D.; Le Roux, Frederique; Lautredou-audouy, Nicole; Got, Patrice; Romestand, Bernard; De Lorgeril, Julien; Kieffer-jaquinod, Sylvie; Bachere, Evelyne; Destoumieux-garzon, Delphine.
OmpU porins are increasingly recognized as key determinants of pathogenic host Vibrio interactions. Although mechanisms remain incompletely understood, various species, including the human pathogen Vibrio cholera, require OmpU for host colonization and virulence. We have shown previously that OmpU is essential for virulence in the oyster pathogen Vibrio splendidus LGP32. Here, we showed that V. splendidus LGP32 invades the oyster immune cells, the hemocytes, through subversion of host-cell actin cytoskeleton. In this process, OmpU serves as an adhesin/invasin required for beta-integrin recognition and host cell invasion. Furthermore, the major protein of oyster plasma, the extracellular superoxide dismutase Cg-EcSOD, is used as an opsonin mediating the...
Tipo: Text Palavras-chave: Host-pathogen interaction; Innate immunity; Invertebrate; Mollusk; Oxidative burst.
Ano: 2011 URL: http://archimer.ifremer.fr/doc/00031/14177/12166.pdf
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The Ancestral N-Terminal Domain of Big Defensins Drives Bacterially Triggered Assembly into Antimicrobial Nanonets ArchiMer
Loth, Karine; Vergnes, Agnes; Barreto, Cairé; Voisin, Sébastien N; Meudal, Hervé; Da Silva, Jennifer; Bressan, Albert; Belmadi, Nawal; Bachère, Evelyne; Aucagne, Vincent; Cazevielle, Chantal; Marchandin, Hélène; Rosa, Rafael Diego; Bulet, Philippe; Touqui, Lhousseine; Delmas, Agnès F.; Destoumieux-garzón, Delphine.
Big defensins, ancestors of β-defensins, are composed of a β-defensin-like C-terminal domain and a globular hydrophobic ancestral N-terminal domain. This unique structure is found in a limited number of phylogenetically distant species, including mollusks, ancestral chelicerates, and early-branching cephalochordates, mostly living in marine environments. One puzzling evolutionary issue concerns the advantage for these species of having maintained a hydrophobic domain lost during evolution toward β-defensins. Using native ligation chemistry, we produced the oyster Crassostrea gigas BigDef1 (Cg-BigDef1) and its separate domains. Cg-BigDef1 showed salt-stable and broad-range bactericidal activity, including against multidrug-resistant human clinical isolates...
Tipo: Text Palavras-chave: MRSA; Antimicrobial peptides; Antimicrobial resistance; Defensins; Fibrils; Innate immunity; Mechanisms of action; Nuclear magnetic resonance.
Ano: 2019 URL: https://archimer.ifremer.fr/doc/00588/70057/68000.pdf
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Glabralysins, Potential New β-Pore-Forming Toxin Family Members from the Schistosomiasis Vector Snail Biomphalaria glabrata ArchiMer
Lassalle, Damien; Tetreau, Guillaume; Pinaud, Silvain; Galinier, Richard; Crickmore, Neil; Gourbal, Benjamain; Duval, David.
Biomphalaria glabrata is a freshwater Planorbidae snail. In its environment, this mollusk faces numerous microorganisms or pathogens, and has developed sophisticated innate immune mechanisms to survive. The mechanisms of recognition are quite well understood in Biomphalaria glabrata, but immune effectors have been seldom described. In this study, we analyzed a new family of potential immune effectors and characterized five new genes that were named Glabralysins. The five Glabralysin genes showed different genomic structures and the high degree of amino acid identity between the Glabralysins, and the presence of the conserved ETX/MTX2 domain, support the hypothesis that they are pore-forming toxins. In addition, tertiary structure prediction confirms that...
Tipo: Text Palavras-chave: Pore-forming toxin; Cry toxin; Invertebrate; Biomphalaria glabrata; Host; Pathogen; Vector snail; Innate immunity.
Ano: 2020 URL: https://archimer.ifremer.fr/doc/00601/71267/69655.pdf
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Comportements cellulaires et régulation génétique au cours des réactions d'immunité innée chez la moule Mytilus galloprovincialis ArchiMer
Li, Hui.
The mytiliculture is one of the most important aquaculture in the world, however, little is known on the mussel immune system, which plays a critical role in case of infectious diseases. Like all the other invertebrates, our model, the Mediterranean mussel Mytilus galloprovincialis, possesses only an innate immune system considered to be primitive and non-specific. In the present study, our results showed that the mussel immune system (i) is capable of responding differently to a variety of stimulations, suggesting a specific recognition process; (ii) reacts differently according to the geographic origin of the animals, showing an adaptation to their own environment; (iii) is influenced by the season, which explains the seasonal mortalities; (iv) presents...
Tipo: Text Palavras-chave: Mytilus; Haemocyte; Antimicrobial peptides; Polymorphism; Genetic regulation; Innate immunity; Mytilus; Hémocyte; Peptides antimicrobiens; Polymorphisme; Régulation génétique; Immunité innée.
Ano: 2008 URL: http://archimer.ifremer.fr/doc/2008/these-6241.pdf
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Influence of temperature, salinity and E. coli tissue content on immune gene expression in mussel: Results from a 2005-2008 survey ArchiMer
Li, Hui; Toubiana, Mylene; Monfort, Patrick; Roch, Philippe.
Several bivalves, including mussels, suffered from mortalities particularly in summer. To look for the possible effect of environmental parameters on immune capacities, Mytilus galloprovincialis were collected monthly from August 2005 to July 2008 from the Palavas Laguna, French Mediterranean coast. Q-PCR was used to quantify the expression of three antimicrobial peptide genes (defensin, mytilin B and myticin B), in addition to lysozyme and HSP70. House keeping gene was 28S rRNA. Defensin, myticin B and lysozyme appeared more expressed in spring-summer than in winter. In contrast, HSP70 expression was higher in winter. Statistical studies using principal component analysis (PCA) and multiple regression models revealed positive influence of temperature on...
Tipo: Text Palavras-chave: Mollusks; Mytilus; Innate immunity; Seasonal variations; Immune survey; Q PCR; HSP70; Lysozyme; Myticin; Mytilin; Defensin; Antimicrobial peptide.
Ano: 2009 URL: http://archimer.ifremer.fr/doc/2009/publication-7345.pdf
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Inefficient immune response is associated with microbial permissiveness in juvenile oysters affected by mass mortalities on field ArchiMer
De Lorgeril, Julien; Escoubas, Jean Michel; Loubiere, Vincent; Pernet, Fabrice; Le Gall, Patrik; Vergnes, Agnes; Aujoulat, Fabien; Jeannot, Jean-luc; Jumas-bilak, Estelle; Got, Patrice; Gueguen, Yannick; Destoumieux-garzon, Delphine; Bachere, Evelyne.
Since 2008, juvenile Crassostrea gigas oysters have suffered from massive mortalities in European farming areas. This disease of complex etiology is still incompletely understood. Triggered by an elevated seawater temperature, it has been associated to infections by a herpes virus named OsHV-1 as well as pathogenic vibrios of the Splendidus clade. Ruling out the complexity of the disease, most of our current knowledge has been acquired in controlled experiments. Among the many unsolved questions, it is still ignored what role immunity plays in the capacity oysters have to survive an infectious episode. Here we show that juvenile oysters susceptible to the disease mount an inefficient immune response associated with microbial permissiveness and death. We...
Tipo: Text Palavras-chave: Host pathogen interaction; Innate immunity; Invertebrate; Mollusk; In situ mortality; Total bacteria; Crassostrea gigas.
Ano: 2018 URL: https://archimer.ifremer.fr/doc/00433/54470/55845.pdf
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Immunotherapeutic potential of Crotoxin: anti-inflammatory and immunosuppressive properties J. Venom. Anim. Toxins incl. Trop. Dis.
Sartim,Marco Aurélio; Menaldo,Danilo Luccas; Sampaio,Suely Vilela.
Abstract For the past 80 years, Crotoxin has become one of the most investigated isolated toxins from snake venoms, partially due to its major role as the main toxic component in the venom of the South American rattlesnake Crotalus durissus terrificus. However, in the past decades, progressive studies have led researchers to shift their focus on Crotoxin, opening novel perspectives and applications as a therapeutic approach. Although this toxin acts on a wide variety of biological events, the modulation of immune responses is considered as one of its most relevant behaviors. Therefore, the present review describes the scientific investigations on the capacity of Crotoxin to modulate anti-inflammatory and immunosuppressive responses, and its application as...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Crotalus durissus terrificus; Crotoxin; Innate immunity; Adaptative immunity; Inflammation.
Ano: 2018 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992018000100329
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