title: Herpes simplex virus type-1-induced activation of myeloid dendritic cells: the roles of virus cell interaction and paracrine type I IFN secretion.
abstract: Adaptive cellular immunity is required to clear HSV-1 infection in the periphery. Myeloid dendritic cells (DCs) are the first professional Ag-presenting cell to encounter the virus after primary and secondary infection and thus the consequences of their infection are important in understanding the pathogenesis of the disease and the response to the virus. Following HSV-1 infection, both uninfected and infected human DCs acquire a more mature phenotype. In this study, we demonstrate that type I IFN secreted from myeloid DC mediates bystander activation of the uninfected DCs. Furthermore, we confirm that this IFN primes DCs for elevated IL-12 p40 and p70 secretion. However, secretion of IFN is not responsible for the acquisition of a mature phenotype by HSV-1-infected DC. Rather, virus binding to a receptor on the cell surface induces DC maturation directly, through activation of the NF-kappaB and p38 MAPK pathways. The binding of HSV glycoprotein D is critical to the acquisition of a mature phenotype and type I IFN secretion. The data therefore demonstrate that DCs can respond to HSV exposure directly through recognition of viral envelope structures. In the context of natural HSV infection, the coupling of viral entry to the activation of DC signaling pathways is likely to be counterbalanced by viral disruption of DC maturation. However, the parallel release of type I IFN may result in paracrine activation so that the DCs are nonetheless able to mount an adaptive immune response.
authors.affiliation: Department of Immunology and Molecular Pathology, University College London, UK.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pollara
authors.forename: Meleri
authors.initials: M
authors.lastname: Jones
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Handley
authors.forename: Mansi
authors.initials: M
authors.lastname: Rajpopat
authors.forename: Antonia
authors.initials: A
authors.lastname: Kwan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Coffin
authors.forename: Graham
authors.initials: G
authors.lastname: Foster
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chain
authors.forename: David R
authors.initials: DR
authors.lastname: Katz
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D000998:Antiviral Agents / Q000502:physiology; D051940:B7-2 Antigen; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D004789:Enzyme Activation / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D009500:Neutralization Tests; D019899:Paracrine Communication / Q000276:immunology*; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000276:immunology; D014759:Viral Envelope Proteins / Q000502:physiology; D038301:Virus Inactivation / Q000528:radiation effects; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D015703:Antigens, CD; D000998:Antiviral Agents; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases