Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment

Immunity. 2006 Jun;24(6):801-12. doi: 10.1016/j.immuni.2006.04.008.

Abstract

Toll-like receptors (TLRs) are best known for their ability to recognize microbial or viral components and initiate innate immune responses. We showed here that TLRs and their coreceptors were expressed by multipotential hematopoietic stem cells, whose cell cycle entry was triggered by TLR ligation. TLR expression also extended to some of the early hematopoietic progenitors, although not the progenitor cells dedicated to megakaryocyte and erythroid differentiation. TLR signaling via the Myd88 adaptor protein drove differentiation of myeloid progenitors, bypassing some normal growth and differentiation requirements, and also drove lymphoid progenitors to become dendritic cells. CD14 contributed to the efficiency of lipopolysaccharide (LPS) recognition by stem and progenitor cells, and LPS interacted directly with the TLR4/MD-2 complex on these cells in bone marrow. Thus, the preferential pathogen-mediated stimulation of myeloid differentiation pathways may provide a means for rapid replenishment of the innate immune system during infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Differentiation
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Granulocytes / cytology
  • Granulocytes / immunology
  • Hematopoietic Stem Cells / chemistry
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • Immunity, Innate*
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / immunology
  • Mice
  • Multipotent Stem Cells / chemistry
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / immunology*
  • Myeloid Differentiation Factor 88
  • Myeloid Progenitor Cells / chemistry
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / immunology
  • Signal Transduction
  • Toll-Like Receptor 4 / analysis
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptors / analysis
  • Toll-Like Receptors / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Lipopolysaccharides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Toll-Like Receptors