Priming of NK Cell Anti-Viral Effector Mechanisms by Direct Recognition of Human Cytomegalovirus
Muntasell i Castellví, Aura 1972- (Institut Hospital del Mar d'Investigacions Mèdiques)
Costa-Garcia, Marcel (Universitat Pompeu Fabra)
Vera, Andrea (Institut Hospital del Mar d'Investigacions Mèdiques)
Marina-Garcia, Noemí (Universitat Pompeu Fabra)
Kirschning, Carsten J. (Institute of Medical Microbiology, University of Duisburg-Essen)
López-Botet, Miguel (Universitat Pompeu Fabra)
Universitat Autònoma de Barcelona

Fecha:	2013
Resumen:	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.
Nota:	Altres ajuts: We thank Dr. Carsten Kirschning for generously providing the blocking mAb anti-TLR2 and Dr. Daniela Pende for providing mAbs for NKp30 and NKp46. We are grateful to Esther Menoyo for collaborating in the obtention of blood samples, Dr. Oscar Fornas for advice in flow cytometry and to all volunteer blood donors. 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).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	NK cells ; HCMV ; Pathogen-associated pattern recognition receptors
Publicado en:	Frontiers in immunology, Vol. 4 (february 2013) , ISSN 1664-3224

DOI: 10.3389/fimmu.2013.00040
PMID: 23440148

10 p, 2.2 MB

El registro aparece en las colecciones:
Artículos > Artículos de investigación
Artículos > Artículos publicados