title: Primary human mDC1, mDC2, and pDC dendritic cells are differentially infected and activated by respiratory syncytial virus.
abstract: Respiratory syncytial virus (RSV) causes recurrent infections throughout life. Vaccine development may depend upon understanding the molecular basis for induction of ineffective immunity. Because dendritic cells (DCs) are critically involved in early responses to infection, their interaction with RSV may determine the immunological outcome of RSV infection. Therefore, we investigated the ability of RSV to infect and activate primary mDCs and pDCs using recombinant RSV expressing green fluorescent protein (GFP). At a multiplicity of infection of 5, initial studies demonstrated ∼6.8% of mDC1 and ∼0.9% pDCs were infected. We extended these studies to include CD1c(-)CD141(+) mDC2, finding mDC2 infected at similar frequencies as mDC1. Both infected and uninfected cells upregulated phenotypic markers of maturation. Divalent cations were required for infection and maturation, but maturation did not require viral replication. There is evidence that attachment and entry/replication processes exert distinct effects on DC activation. Cell-specific patterns of RSV-induced maturation and cytokine production were detected in mDC1, mDC2, and pDC. We also demonstrate for the first time that RSV induces significant TIMP-2 production in all DC subsets. Defining the influence of RSV on the function of selected DC subsets may improve the likelihood of achieving protective vaccine-induced immunity.
authors.affiliation: Viral Pathogenesis Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Bethesda, Maryland, United States of America. teresaj@nih.gov
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Johnson
authors.forename: Christina N
authors.initials: CN
authors.lastname: Johnson
authors.forename: Kizzmekia S
authors.initials: KS
authors.lastname: Corbett
authors.forename: Gretchen C
authors.initials: GC
authors.lastname: Edwards
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D055633:Immune System Phenomena; D016130:Immunophenotyping; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D019716:Tissue Inhibitor of Metalloproteinase-2