RESUMO
Iron homeostasis is vital to organismal health; it is maintained by the iron regulatory protein (IRP)-iron-responsive element (IRE) signaling pathway. In the Chinese mitten crab Eriocheir sinensis, EsFer-1 and EsFer-2 reportedly have a putative IRE, but an IRP has not yet been identified. In this study, we successfully amplified the full-length cDNA of EsIRP using gene cloning and rapid amplification of cDNA ends techniques. The length of this cDNA was 4474 bp, and it included a 2682-bp open reading frame encoding 893 amino acids. Using quantitative real-time PCR, mRNA transcripts of EsIRP were detected in various tissues. The highest and lowest expression level was detected in the muscle and gills, respectively. In response to Staphylococcus aureus and Vibrio parahaemolyticus challenge, the transcription level of EsIRP was downregulated and that of EsFer-1 and EsFer-2 was upregulated in hemocytes. EsIRP knockdown resulted in increased expression of both EsFer-1 and EsFer-2. After EsFer-1 and EsFer-2 knockdown, the bacterial clearance ability of E. sinensis against S. aureus and V. parahaemolyticus was impaired. In conclusion, our results suggest that the IRP-IRE signaling pathway plays an important role in the innate immune system response in E. sinensis.
Assuntos
Braquiúros/genética , Braquiúros/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteínas Reguladoras de Ferro/genética , Proteínas Reguladoras de Ferro/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Perfilação da Expressão Gênica , Proteínas Reguladoras de Ferro/química , Masculino , Filogenia , Alinhamento de Sequência , Staphylococcus aureus/fisiologia , Vibrio parahaemolyticus/fisiologiaRESUMO
Iron is an essential trace element for multicellular organisms and nearly all microorganisms. Although iron is abundant in the environment, common forms of iron are minimally soluble and therefore poorly accessible to biological organisms. Microorganisms entering a mammalian host face multiple mechanisms that further restrict their ability to obtain iron and thereby limit their pathogenicity. Iron levels also modulate host defence, as iron content in macrophages regulates their cytokine production. Here, we review recent advances that highlight the role of systemic and cellular iron-regulating mechanisms in protecting hosts from infection, emphasizing aspects that are applicable to human health and disease.
Assuntos
Infecções Bacterianas/imunologia , Homeostase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Proteínas Reguladoras de Ferro/imunologia , Ferro/imunologia , Ferroproteínas não Heme/imunologia , Animais , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Citocinas/genética , Citocinas/imunologia , Regulação da Expressão Gênica , Humanos , Imunidade Inata , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Ferro/metabolismo , Proteínas de Ligação ao Ferro/genética , Proteínas Reguladoras de Ferro/genética , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Ferroproteínas não Heme/genética , Transdução de SinaisRESUMO
Staphylococcus aureus is an important pathogen that is responsible for a wide range of infections, including bovine mastitis. Previously, 54 genes from S. aureus that were up-regulated in an iron-restricted medium and in mice were identified. Seven of those genes were selected from five iron-acquisition systems (isd, feo, sir, sst, and fhu), and the proteins were evaluated as potential vaccine targets to prevent bovine mastitis. The antigenicity of the recombinant proteins obtained with each studied gene was evaluated in rabbits and/or cattle. Immune sera were used to test the bacterial accessibility of the native proteins. All the proteins were immunogenic in rabbits or cattle. IsdH, IsdB, FeoB and SstD were expressed on the bacterial surface, with IsdB and IsdH more expressed in an iron-restricted environment. The capacity of antibodies to prevent infection was measured in a mouse mastitis model. Preincubation of S. aureus with serum against IsdH or with the pool of sera against IsdB, SstD and FeoB led to decreased colonization of the mouse mammary glands. Lastly, cattle immunization with IsdH induced a strong and long-lasting immune response with IgG2 production. The protein IsdH appears to be a good vaccine candidate to prevent S. aureus bovine mastitis.
Assuntos
Proteínas Reguladoras de Ferro/imunologia , Mastite Bovina/microbiologia , Proteínas Recombinantes/imunologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/imunologia , Animais , Bovinos , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Imunização/métodos , Imunização/veterinária , Imunoglobulina G/imunologia , Isotipos de Imunoglobulinas/imunologia , Masculino , Mastite Bovina/imunologia , Mastite Bovina/prevenção & controle , Coelhos , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologiaRESUMO
Hepcidin, originally identified as a 25 amino acid peptide antibiotic produced in the liver, is a key regulator of iron balance and recycling in humans and mice. Closely related hepcidin genes and peptides also have been identified in other mammals, amphibians, and a number of fish species. We hypothesize that hepcidin, the iron-regulatory hormone in humans, may have evolved from an antimicrobial peptide in fishes. In this review we will highlight the evidence that indicates hepcidin evolved from an antimicrobial peptide to an iron-regulatory hormone in vertebrate evolution. This evidence includes the discovery of hepcidin as an antimicrobial peptide and iron-regulatory hormone, structural comparison of mammalian hepcidins and nonmammalian hepcidins, and the cellular and molecular evidence indicating that, while some fish hepcidins may serve only as antimicrobial peptides, other fish and amphibian hepcidins may function as iron regulators.
