title: Dendritic cell dysregulation during HIV-1 infection.
abstract: Dendritic cells (DCs) are a diverse subset of innate immune cells that are key regulators of the host response to human immunodeficiency virus-1 (HIV-1) infection. HIV-1 directly and indirectly modulates DC function to hinder the formation of effective antiviral immunity and fuel immune activation. This review focuses upon the differential dysregulation of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) at various stages of HIV-1 infection providing insights into pathogenesis. HIV-1 evades innate immune sensing by mDCs resulting in suboptimal maturation, lending to poor generation of antiviral adaptive responses and contributing to T-regulatory cell (Treg) development. Dependent upon the stage of HIV-1 infection, mDC function is altered in response to Toll-like receptor ligands, which further hinders adaptive immunity and limits feasibility of therapeutic vaccine strategies. pDC interactions with HIV-1 are pleotropic, modulating immune responses on an axis between immunostimulatory and immunosuppressive. pDCs promote immune activation through an altered phenotype of persistent type I interferon secretion and weak antigen presentation capacity. Conversely, HIV-1 stimulates secretion of indolemine 2,3 dioxygenase (IDO) by pDCs resulting in Treg induction. An improved understanding of the roles and underlying mechanisms of DC dysfunction will be valuable to the development of therapeutics to enhance HIV-specific adaptive responses and to dampen immune activation.
authors.affiliation: Division of Infectious Diseases, New York University School of Medicine, New York, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
authors.forename: Nina
authors.initials: N
authors.lastname: Bhardwaj
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation