Bacterial DNA and Immunostimulatory CpG Oligonucleotides Trigger Maturation and Activation of Murine Dendritic Cells

Eur J Immunol. 1998 Jun;28(6):2045-54. doi: 10.1002/(SICI)1521-4141(199806)28:06<2045::AID-IMMU2045>3.0.CO;2-8.

Abstract

Bacterial DNA and immunostimulatory (i.s.) synthetic CpG-oligodeoxynucleotides (ODN) act as adjuvants for Th1 responses and cytotoxic T cell responses to proteinaceous antigens. Dendritic cells (DC) can be referred to as "nature's adjuvant" since they display the unique capacity to sensitize naive T cells. Here, we demonstrate that bacterial DNA or i.s. CpG-ODN cause simultaneous maturation of immature DC and activation of mature DC to produce cytokines. These events are associated with the acquisition of professional antigen-presenting cell (APC) function. Unfractionated murine bone marrow-derived DC and FACS-fractionated MHC class IIlow (termed immature DC) or MHC class IIhigh populations (termed mature DC) were stimulated with bacterial DNA or i.s. CpG-ODN. Similar to lipopolysaccharide, i.s. CpG-ODN caused up-regulation of MHC class II, CD40 and CD86, but not CD80 on immature and mature DC. In parallel both DC subsets were activated to produce large amounts of IL-12, IL-6 and TNF-alpha. CpG-ODN-activated DC displayed professional APC function in allogeneic mixed lymphocyte reaction and in staphylococcal enterotoxin B-driven naive T cell responses. We interpret these findings to mean that bacterial DNA and i.s. CpG-ODN cause maturation (first step) and activation (second step) of DC to bring about conversion of immature DC into professional APC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Bone Marrow Cells
  • CD40 Antigens / metabolism
  • Cells, Cultured
  • CpG Islands / immunology*
  • DNA, Bacterial / immunology*
  • Dendritic Cells / immunology*
  • Enzyme Induction
  • Female
  • HLA-B7 Antigen / metabolism
  • Hematopoiesis
  • Histocompatibility Antigens Class II / metabolism
  • Interleukin-12 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligodeoxyribonucleotides / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Up-Regulation
  • beta-Galactosidase / metabolism

Substances

  • Adjuvants, Immunologic
  • CD40 Antigens
  • DNA, Bacterial
  • HLA-B7 Antigen
  • Histocompatibility Antigens Class II
  • Interleukin-6
  • Oligodeoxyribonucleotides
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • beta-Galactosidase