Dermal-Type Macrophages Expressing CD209/DC-SIGN Show Inherent Resistance to Dengue Virus Growth.

Wing-Hong Kwan (1, 2) , Erika Navarro-Sanchez (3, 4) , Hélène Dumortier (1) , Marion Decossas (1) , Hortense Vachon (1, 5) , Flavia Barreto dos Santos (6) , Hervé W Fridman (2) , Félix A. Rey (4) , Eva Harris (6) , Philippe Desprès (3) , Christopher G Mueller (1)

1 ICT - Immunologie et chimie thérapeutiques
2 CRC (UMR_S 872) - Centre de Recherche des Cordeliers
3 Interactions Moléculaires Flavivirus-Hôtes
4 Virologie Structurale
5 TGML - Transcriptomics and Genomics of Marseille-Luminy
6 Division of Infectious Diseases

BACKGROUND: An important question in dengue pathogenesis is the identity of immune cells involved in the control of dengue virus infection at the site of the mosquito bite. There is evidence that infection of immature myeloid dendritic cells plays a crucial role in dengue pathogenesis and that the interaction of the viral envelope E glycoprotein with CD209/DC-SIGN is a key element for their productive infection. Dermal macrophages express CD209, yet little is known about their role in dengue virus infection. METHODS AND FINDINGS: Here, we showed that dermal macrophages bound recombinant envelope E glycoprotein fused to green fluorescent protein. Because dermal macrophages stain for IL-10 in situ, we generated dermal-type macrophages from monocytes in the presence of IL-10 to study their infection by dengue virus. The macrophages were able to internalize the virus, but progeny virus production was undetectable in the infected cells. In addition, no IFN-alpha was produced in response to the virus. The inability of dengue virus to grow in the macrophages was attributable to accumulation of internalized virus particles into poorly-acidified phagosomes. CONCLUSIONS: Aborting infection by viral sequestration in early phagosomes would present a novel means to curb infection of enveloped virus and may constitute a prime defense system to prevent dengue virus spread shortly after the bite of the infected mosquito.

Domaines: Maladies infectieuses

Wing-Hong Kwan, Erika Navarro-Sanchez, Hélène Dumortier, Marion Decossas, Hortense Vachon, et al.. Dermal-Type Macrophages Expressing CD209/DC-SIGN Show Inherent Resistance to Dengue Virus Growth.. PLoS Neglected Tropical Diseases, 2008, 2 (10), pp.e311. ⟨10.1371/journal.pntd.0000311⟩. ⟨hal-00335138⟩