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Md1 and Rp105 regulate innate immunity and viral resistance in zebrafish

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dc.contributor.authorCandel, Sergio
dc.contributor.authorSepulcre, María P.
dc.contributor.authorEspín-Palazón, Raquel
dc.contributor.authorTyrkalska, Sylwia D.
dc.contributor.authorDe Oliveira, Sofia
dc.contributor.authorMeseguer, José
dc.contributor.authorMulero, Victoriano
dc.date.accessioned2020-11-20T16:42:14Z
dc.date.available2020-11-20T16:42:14Z
dc.date.issued2015
dc.description© 2015 Elsevier Ltd. All rights reserved.pt_PT
dc.description.abstractTLR4 was the first TLR family member identified in mammals and is responsible for the activation of the immune response by bacterial LPS. Later, MD1 and RP105 were shown to form complexes that directly interact with the MD2-TLR4 complex, acting as physiological negative regulators of LPS signaling. Despite the general conservation of various TLR families from fish to mammals, several differences can be appreciated, such as the high tolerance of fish to LPS, the absence of the crucial accessory molecules Md2 and Cd14 for Tlr4 signaling in fish, the absence of Tlr4 in some fish species, and the confirmation that LPS does not signal through Tlr4 in zebrafish. The present study has identified the Rp105 and Md1 homologs in zebrafish, confirming (i) Rp105 and Tlr4 evolved from a common ancestor before the divergence between fish and tetrapods and (ii) the presence of Md1 in teleost fish and the lack of Md2, suggesting that the divergence of these accessory molecules occurred in the tetrapod lineage. Biochemical and functional studies indicate that Md1 binds both Rp105 and Tlr4 in zebrafish. Genetic inhibition of zebrafish Md1 and Rp105 reveals that Md1 or Rp105 deficiency impairs the expression of genes encoding pro-inflammatory and antiviral molecules, leading to increased susceptibility to viral infection. These results shed light on the evolutionary history of Md1 and Rp105 and uncover a previously unappreciated function of these molecules in the regulation of innate immunity.pt_PT
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Scienceand Innovation (grants BIO2011-23400 and CSD2007-00002 to VM,and PhD fellowship to SC, all co-funded with Fondos Europeos de Desarrollo Regional/European Regional Development Funds), the Fundación Séneca-Murcia (PhD fellowship to RE-P), the European7th Framework Initial Training Network Fish For Pharma (PhD fellowship to SDT, PITG-GA-2011-289209), and Fundação para a Ciência e Tecnologia (PhD fellowship to SdO, SFRH/BD/62674/2009).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationDev Comp Immunol. 2015 Jun;50(2):155-65pt_PT
dc.identifier.doi10.1016/j.dci.2015.01.005pt_PT
dc.identifier.issn0145-305X
dc.identifier.urihttp://hdl.handle.net/10451/44951
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationBIO2011-23400pt_PT
dc.relationCSD2007-00002pt_PT
dc.relationPITG-GA-2011-289209pt_PT
dc.relationIN VIVO IMAGING OF INFLAMMATION IN ZEBRAFISH: THE ROLE OF CHEMOKINE SYSTEM IN NEUTROPHIL AND MACROPHAGE MIGRATION
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/developmental-and-comparative-immunologypt_PT
dc.subjectEvolutionpt_PT
dc.subjectInterferonspt_PT
dc.subjectLPSpt_PT
dc.subjectTeleostspt_PT
dc.subjectToll-like receptorspt_PT
dc.titleMd1 and Rp105 regulate innate immunity and viral resistance in zebrafishpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIN VIVO IMAGING OF INFLAMMATION IN ZEBRAFISH: THE ROLE OF CHEMOKINE SYSTEM IN NEUTROPHIL AND MACROPHAGE MIGRATION
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F62674%2F2009/PT
oaire.citation.endPage165pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage155pt_PT
oaire.citation.titleDevelopmental & Comparative Immunologypt_PT
oaire.citation.volume50pt_PT
person.familyNameDe Oliveira
person.givenNameSofia
person.identifier1026730
person.identifier.ciencia-id7011-768C-81B6
person.identifier.orcid0000-0003-0893-111X
person.identifier.scopus-author-id24476411300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication007f8d3b-8acf-47bd-8eb8-b8f33d6b9d2b
relation.isAuthorOfPublication.latestForDiscovery007f8d3b-8acf-47bd-8eb8-b8f33d6b9d2b
relation.isProjectOfPublication66b32d6f-6829-43b7-a33d-4c39801b18a1
relation.isProjectOfPublication.latestForDiscovery66b32d6f-6829-43b7-a33d-4c39801b18a1

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