Vaccinia virus infection induces dendritic cell maturation but inhibits antigen presentation by MHC class II

Abstract

Vaccinia virus (VV) infection is known to inhibit dendritic cells (DC) functions in vitro.Paradoxically, VV is also highly immunogenic and thus has been used as a vaccine. In the present study, we investigated the effects of an in vivo VV infection on DC function by focusing on early innate immunity. Our data indicated that DC are activated upon in vivo VV infection of mice. Splenic DC from VV-infected mice expressed elevated levels of MHC class I and co-stimulatory molecules on their cell surface and exhibited the enhanced potential to produce cytokines upon LPS stimulation. DC from VV-infected mice also expressed a high level of interferon-β. However, a VV infection resulted in the down-regulation of MHC class II expression and the impairment of antigen presentation to CD4 T cells by DC. Thus, during the early stage of a VV infection, although DC are impaired in some of the critical antigen presentation functions, they can promote innate immune defenses against viral infection.

Cytokine-armed vaccinia virus infects the mesothelioma tumor microenvironment to overcome immune tolerance and mediate tumor resolution

“…Thus, proteosomal degradation may have prevented HA expression and resolved DC infection. However, in agreement with the earlier reports, DC maturation did not occur after infection by the VV constructs implying reduced antigen-presenting function [46][47][48][49] and indicating a potentially detrimental bystander response after i.t. VV.…”

Interplay between Modified Vaccinia Virus Ankara and Dendritic Cells: Phenotypic and Functional Maturation of Bystander Dendritic Cells

“…Since we have not formally proven charging of MHC with virally expressed antigen, it could be argued that processing and presentation of antigens could be impaired by MVA. This has been demonstrated for the presentation of antigens by MHC class II molecules after VV infection (30,40,48), and Behboudi et al (4) described downregulation of class I molecules in mouse DCs after infection with MVA. However, we did not observe class I molecule downregulation in human DCs.…”

“…Maturation of DCs is a fundamental step before the generation of an adaptive immune response. Since VV is highly immunogenic, it would be expected to induce maturation of DCs in vivo, and in fact, this has been demonstrated to occur in a mouse model (48). Unlike VV, and as a consequence of attenuation, MVA was shown to induce maturation of human DCs in vitro, evidenced as moderate increase in cell surface CD80 and CD83, a more marked increase in CD86, and production of low levels of tumor necrosis factor alpha (TNF-␣) and interleukin 6 (IL-6) (17).…”

Effects of Herpes Simplex Virus Amplicon Transduction on Murine Dendritic Cells

“…Besides HSV amplicon, transduction of DCs with lentiviral vectors (Koya et al, 2003) and vaccinia virus (Yao et al, 2007) also induces DC maturation. It is noteworthy that our current study demonstrates that HSV amplicon transduction promotes a transient ''maturation-like'' process in DCs (Fig.…”

“…Yao and colleagues (2007) showed that vaccinia viral (VV) infection causes an upregulation of MHCI but a downregulation of MHCII on DCs in live animals (Yao et al, 2007). Together, these data suggested that VV and amplicon might employ different mechanisms in modulating the antigen presentation activity of iDCs as represented by their variations in regulating surface MHCII expression.…”