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* Laboratoire d’Immunochimie, Institut National de la Santé et de la Recherche Médicale Unité 548; Commissariat à l’Energie Atomique; and Université Joseph Fourier, Grenoble, France;
Institut National de la Santé et de la Recherche Médicale Unité 503; Université Lyon 1; and Institut Fédératif de Recherche 128-Biosciences Gerland, Lyon, France; and
bioMérieux, Research and Development, Marcy l’Etoile, France
Multiple sclerosis-associated retroviral element (MSRV) is a retroviral element, the sequence of which served to define the W family of human endogenous retroviruses. MSRV viral particles display proinflammatory activities both in vitro in human mononuclear cell cultures and in vivo in a humanized SCID mice model. To understand the molecular basis of such properties, we have investigated the inflammatory potential of the surface unit of the MSRV envelope protein (ENV-SU), the fraction that is poised to naturally interact with host cells. We report in this study that MSRV ENV-SU induces, in a specific manner, human monocytes to produce major proinflammatory cytokines through engagement of CD14 and TLR4, which are pattern recognition receptors of primary importance in innate immunity. ENV-SU could also trigger a maturation process in human dendritic cells. Finally, ENV-SU endowed dendritic cells with the capacity to support a Th1-like type of Th cell differentiation. The data are discussed in the context of immune responses and chronic proinflammatory disorders.
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