title: The effect of human immunodeficiency virus-1 on monocyte-derived dendritic cell maturation and function.
abstract: Dendritic cells (DC) are mediators of the adaptive immune response responsible for antigen presentation to naive T cells in secondary lymph organs. Human immunodeficiency virus (HIV-1) has been reported to inhibit the maturation of DC, but a clear link between maturation and function has not been elucidated. To understand further the effects of HIV-1 on DC maturation and function, we expanded upon previous investigations and assessed the effects of HIV-1 infection on the expression of surface molecules, carbohydrate endocytosis, antigen presentation and lipopolysaccharide (LPS) responsiveness over the course of maturation. In vitro infection with HIV-1 resulted in an increase in the expression of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) as well as decreases in maturation-induced CCR7 and major histocompatibility complex (MHC)-II expression. Retention of endocytosis that normally occurs with DC maturation as well as inhibition of antigen presentation to CD8(+)  T cells was also observed. Mitogen-activated protein kinase (MAPK) responsiveness to LPS as measured by phosphorylation of p38, c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK)1/2 was not affected by HIV-1 infection. In summary, in-vitro HIV-1 impairs DC maturation, as defined by cell surface protein expression, with selective alterations in mature DC function. Understanding the mechanisms of DC dysfunction in HIV infection will provide further insight into HIV immune pathogenesis.
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Fairman
authors.forename: J B
authors.initials: JB
authors.lastname: Angel
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004705:Endocytosis / Q000276:immunology; D005802:Genes, MHC Class II; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000821:virology; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D054400:Receptors, CCR7 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D048031:JNK Mitogen-Activated Protein Kinases; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D048051:p38 Mitogen-Activated Protein Kinases; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C515370:CCR7 protein, human