Priming of NK cell anti-viral effector mechanisms by direct recognition of human cytomegalovirus

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  • dc.contributor.author Muntasell i Castellví, Aura, 1972-ca
  • dc.contributor.author Costa-García, Marcelca
  • dc.contributor.author Vera, Andreaca
  • dc.contributor.author Marina-García, Noemíca
  • dc.contributor.author Kirschning, Carsten J.ca
  • dc.contributor.author López-Botet, M. (Miguel)ca
  • dc.date.accessioned 2015-06-08T08:49:50Z
  • dc.date.available 2015-06-08T08:49:50Z
  • dc.date.issued 2013ca
  • dc.description.abstract Natural killer (NK) cells play an important role in the defense against viral infections. Activation of resting NK cells is tightly controlled by the balance of surface inhibitory and activating receptors and aided by cytokines released by accessory cells along the anti-viral response. On the other hand, NK cells express functional pattern recognition receptors (PRRs) whose function has been mostly addressed by the use of synthetic agonists. The present study was undertaken to investigate whether NK cells could directly recognize a complex pathogen such as Human Cytomegalovirus (HCMV). Exposure of primary human NK cells to HCMV (TB40/E strain) induced the expression of CD69, promoted IFNγ secretion, and increased their cytotoxic activity against HCMV-infected autologous monocyte-derived dendritic cells. The divergent response induced by infective and UV-inactivated virions indicated the involvement of different NK cell sensors in the recognition of HCMV. The fact that NK cell activation could be partially prevented by blocking mAb specific for IFNAR and TLR2, together with the induction of IFNβ mRNA, supported the involvement of IFNβ and TLR2 in the response to HCMV. Thus, our data indicate that simultaneous activation of several PRRs leads to the autonomous priming of NK cell effector functions and could be a previously unappreciated mechanism presumably contributing to the control of HCMV infection.en
  • dc.description.sponsorship This work was supported by grants from Plan Nacional de I + D (SAF2010–22153-C03), and EU SUDOE program (SOE2/P1/E341). Aura Muntasell is supported by Asociación Española Contra el Cáncer (AECC), Andrea Vera is supported by Red HERACLES (Instituto de Salut Carlos III).en
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Muntasell A, Costa-García M, Vera A, Marina-García N, Kirschning CJ, López-Botet M. Priming of NK cell anti-viral effector mechanisms by direct recognition of human cytomegalovirus. Frontiers in Immunology. 2013;4:40. DOI: 10.3389/fimmu.2013.00040ca
  • dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2013.00040
  • dc.identifier.issn 1664-3224ca
  • dc.identifier.uri http://hdl.handle.net/10230/23758
  • dc.language.iso engca
  • dc.publisher Frontiersca
  • dc.relation.ispartof Frontiers in Immunology. 2013;4:40
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-22153
  • dc.rights © 2013 Muntasell, Costa-Garcia, Vera, Marina-Garcia, Kirschning and López-Botet. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.en
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri https://creativecommons.org/licenses/by/3.0/
  • dc.subject.keyword NK cellsen
  • dc.subject.keyword HCMVen
  • dc.subject.keyword Pathogen-associated pattern recognition receptorsen
  • dc.subject.other Cèl·lules citotòxiquesca
  • dc.subject.other Receptors cel·lularsca
  • dc.subject.other Infeccions per citomegalovirusca
  • dc.title Priming of NK cell anti-viral effector mechanisms by direct recognition of human cytomegalovirusen
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca