Open AccessInterplay between Modified Vaccinia Virus Ankara and Dendritic Cells: Phenotypic and Functional Maturation of Bystander Dendritic Cells
Author(s) -
María Fernanda Pascutti,
Ana Rodrı́guez,
Juliana Falivene,
Luis D. Giavedoni,
Ingo Drexler,
M. Magdalena Gherardi
Publication year - 2011
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02267-10
Subject(s) - biology , cd86 , bystander effect , cxcl10 , dendritic cell , vaccinia , chemokine , virology , cd8 , immune system , tumor necrosis factor alpha , immunology , recombinant dna , t cell , gene , biochemistry
Modified vaccinia virus Ankara (MVA) is an attenuated poxvirus strain, currently under evaluation as a vaccine vector in various clinical settings. It has been reported that human dendritic cells (DCs) mature after infection with MVA, but reports on the functionality of DCs have so far been controversial. In this work, we studied the phenotype and functionality of MVA-infected DCs. As previously reported, we found that human monocyte-derived DCs upregulated CD86 and HLA-DR in response to MVA infection. Moreover, infected DCs produced a broad array of chemokines and cytokines and were able to activate and induce gamma interferon (IFN-γ) production both in CD4+ and in CD8+ allogeneic T cells and in specific autologous peripheral blood lymphocytes (PBLs). Analysis of DC maturation following infection with a recombinant green fluorescent protein (GFP)-expressing MVA revealed that upregulation of CD86 expression was mainly observed in GFPneg (bystander) cells. While GFPpos (infected) DCs produced tumor necrosis factor alpha (TNF-α), they were unable to produce CXCL10 and were less efficient at inducing IFN-γ production in CEF-specific autologous PBLs. Maturation of bystander DCs could be achieved by incubation with supernatant from infected cultures or with apoptotic infected cells. Type I IFNs were partially responsible for the induction of CXCL10 on bystander DCs. Our findings demonstrate for the first time that, in MVA-infected DC cultures, the leading role with respect to functionality and maturation characteristics is achieved by the bystander DCs.