Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth.
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.


RESULTS
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.
Kwan
Wing-Hong
WH
CNRS, Laboratory of Therapeutic Immunology and Chemistry, IBMC, Université Louis Pasteur, Strasbourg, France.
Navarro-Sanchez
Erika
E
Dumortier
Hélène
H
Decossas
Marion
M
Vachon
Hortense
H
dos Santos
Flavia Barreto
FB
Fridman
Hervé W
HW
Rey
Félix A
FA
Harris
Eva
E
Despres
Philippe
P
Mueller
Christopher G
CG
D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003715:Dengue / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003716:Dengue Virus / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin