Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells

Nat Immunol. 2009 Jun;10(6):587-94. doi: 10.1038/ni.1733.

Abstract

Little is known of how and where bacterial recognition triggers the induction of type I interferon. Whether the type of recognition receptor used in these responses is determined by the subcellular location of bacteria is not understood. Here we show that phagosomal bacteria such as group B streptococcus, but not cytosolic bacteria, potently induced interferon in conventional dendritic cells by a mechanism that required Toll-like receptor 7, the adaptor MyD88 and the transcription factor IRF1, all of which localized together with bacterial products in degradative vacuoles bearing lysosomal markers. Thus, this cell type-specific recognition pathway links lysosomal recognition of bacterial RNA with a robust, host-protective interferon response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / immunology
  • Animals, Newborn / microbiology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Female
  • Interferon Regulatory Factor-1 / immunology
  • Interferon Regulatory Factor-1 / metabolism
  • Interferon-beta / biosynthesis
  • Lysosomes / immunology
  • Lysosomes / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / immunology
  • Myeloid Differentiation Factor 88 / metabolism
  • Phagocytosis
  • Phagosomes / immunology
  • Phagosomes / metabolism
  • RNA, Bacterial / metabolism
  • Signal Transduction
  • Streptococcal Infections / immunology
  • Streptococcus agalactiae / immunology*
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 7 / metabolism*

Substances

  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • RNA, Bacterial
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Interferon-beta