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Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4.
J Invest Dermatol. 2015 Jul; 135(7):1743-1751.JI

Abstract

Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Laboratory of Immunopathology and Therapeutic Chemistry, CNRS UPR 3572/Laboratory of Excellence MEDALIS, IBMC, University of Strasbourg, Strasbourg, France.

Laboratory of Immunopathology and Therapeutic Chemistry, CNRS UPR 3572/Laboratory of Excellence MEDALIS, IBMC, University of Strasbourg, Strasbourg, France.

Laboratory of Immunopathology and Therapeutic Chemistry, CNRS UPR 3572/Laboratory of Excellence MEDALIS, IBMC, University of Strasbourg, Strasbourg, France.

Laboratory of Immunopathology and Therapeutic Chemistry, CNRS UPR 3572/Laboratory of Excellence MEDALIS, IBMC, University of Strasbourg, Strasbourg, France; Current address: Chemistry and Biology of Membranes and Nanoobjects, CBMN, UMR 5248, CNRS-University of Bordeaux1-IPB, 33600 Pessac, France.

Laboratory of Immunopathology and Therapeutic Chemistry, CNRS UPR 3572/Laboratory of Excellence MEDALIS, IBMC, University of Strasbourg, Strasbourg, France.

Laboratory of Immunopathology and Therapeutic Chemistry, CNRS UPR 3572/Laboratory of Excellence MEDALIS, IBMC, University of Strasbourg, Strasbourg, France.

Laboratory of Immunopathology and Therapeutic Chemistry, CNRS UPR 3572/Laboratory of Excellence MEDALIS, IBMC, University of Strasbourg, Strasbourg, France. Electronic address: c.mueller@ibmc-cnrs.unistra.fr.

MeSH

Abdominal WallAntigen-Presenting CellsCell Adhesion MoleculesCells, CulturedCytokinesDengueDengue VirusEnzyme-Linked Immunosorbent AssayEpidermal CellsHumansInterleukin-4Langerhans CellsLectins, C-TypeLymphocyte ActivationMacrophagesMicroscopy, ConfocalReceptors, Cell SurfaceSensitivity and SpecificitySkin Diseases, Viral

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25521455

Citation

Schaeffer, Evelyne, et al. "Dermal CD14(+) Dendritic Cell and Macrophage Infection By Dengue Virus Is Stimulated By Interleukin-4." The Journal of Investigative Dermatology, vol. 135, no. 7, 2015, pp. 1743-1751.

Schaeffer E, Flacher V, Papageorgiou V, et al. Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4. J Invest Dermatol. 2015;135(7):1743-1751.

Schaeffer, E., Flacher, V., Papageorgiou, V., Decossas, M., Fauny, J. D., Krämer, M., & Mueller, C. G. (2015). Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4. The Journal of Investigative Dermatology, 135(7), 1743-1751. https://doi.org/10.1038/jid.2014.525

Schaeffer E, et al. Dermal CD14(+) Dendritic Cell and Macrophage Infection By Dengue Virus Is Stimulated By Interleukin-4. J Invest Dermatol. 2015;135(7):1743-1751. PubMed PMID: 25521455.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Dermal CD14(+) Dendritic Cell and Macrophage Infection by Dengue Virus Is Stimulated by Interleukin-4. AU - Schaeffer,Evelyne, AU - Flacher,Vincent, AU - Papageorgiou,Vasiliki, AU - Decossas,Marion, AU - Fauny,Jean-Daniel, AU - Krämer,Melanie, AU - Mueller,Christopher G, Y1 - 2014/12/18/ PY - 2014/05/23/received PY - 2014/12/05/revised PY - 2014/11/12/accepted PY - 2014/12/19/entrez PY - 2014/12/19/pubmed PY - 2015/9/8/medline SP - 1743 EP - 1751 JF - The Journal of investigative dermatology JO - J Invest Dermatol VL - 135 IS - 7 N2 - Dengue virus (DENV) is responsible for the most prevalent arthropod-borne viral infection in humans. Events decisive for disease development occur in the skin after virus inoculation by the mosquito. Yet, the role of human dermis-resident immune cells in dengue infection and disease remains elusive. Here we investigated how dermal dendritic cells (dDCs) and macrophages (dMs) react to DENV and impact on immunopathology. We show that both CD1c(+) and CD14(+) dDC subsets were infected, but viral load greatly increased in CD14(+) dDCs upon IL-4 stimulation, which correlated with upregulation of virus-binding lectins Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN/CD209) and mannose receptor (CD206). IL-4 also enhanced T-cell activation by dDCs, which was further increased upon dengue infection. dMs purified from digested dermis were initially poorly infected but actively replicated the virus and produced TNF-α upon lectin upregulation in response to IL-4. DC-SIGN(+) cells are abundant in inflammatory skin with scabies infection or Th2-type dermatitis, suggesting that skin reactions to mosquito bites heighten the risk of infection and subsequent immunopathology. Our data identify dDCs and dMs as primary arbovirus target cells in humans and suggest that dDCs initiate a potent virus-directed T-cell response, whereas dMs fuel the inflammatory cascade characteristic of dengue fever. SN - 1523-1747 UR - https://www.unboundmedicine.com/medline/citation/25521455/Dermal_CD14_+__Dendritic_Cell_and_Macrophage_Infection_by_Dengue_Virus_Is_Stimulated_by_Interleukin_4_ DB - PRIME DP - Unbound Medicine ER -