The tug-of-war between dendritic cells and human chronic viruses (105.47)

Abstract

Abstract The human immune system is under constant challenge from many viruses, some of which the body is successfully able to clear. Other viruses have evolved to escape the host immune responses and thus persist, leading to the development of chronic diseases. Dendritic cells (DCs) are professional antigen presenting cells that play a major role in both innate and adaptive immunity against different pathogens. For the past few years our efforts have been focused on exploring the participation of DCs in the pathogenesis of HTLV-1, HIV-1 and HCV. We observed previously that depletion of DCs in CD11c-DTR transgenic mice enhanced the susceptibility to cell-free HTLV-1 infection. We further performed the host-pathogen interaction studies utilizing Flt3 ligand derived murine bone marrow DCs (FL-DCs). First, the kinetics of viral entry, proviral integration, and expression of the viral protein Tax was established and then effects of cell-free HTLV-1 was examined on these cells. Phenotypically, FL-DCs demonstrated activation and produced an array of proinflammatory cytokines as well as IFN-α. Virus-matured FL-DCs also stimulated proliferation of autologous CD3+ T cells and IFN-γ production. Gene expression studies revealed upregulation of interferon-stimulated genes, most cytokines, and transcription factors but a distinct downregulation of many chemokines. Overall, these results highlight the critical interaction of DCs with a human chronic virus important for the early immune responses.