TLR4 and Toll-IL-1 receptor domain-containing adapter-inducing IFN-beta, but not MyD88, regulate Escherichia coli-induced dendritic cell maturation and apoptosis in vivo

J Immunol. 2005 Jul 15;175(2):839-46. doi: 10.4049/jimmunol.175.2.839.

Abstract

Dendritic cells (DC) are short-lived, professional APCs that play a central role in the generation of adaptive immune responses. Induction of efficient immune responses is dependent on how long DCs survive in the host. Therefore, the regulation of DC apoptosis in vivo during infection remains an important question that requires further investigation. The impact of Escherichia coli bacteremia on DCs has never been analyzed. We show here that i.v. or i.p. administration of live or heat-killed E. coli in mice induces splenic DC migration, maturation, and apoptosis. We further characterize which TLR and Toll-IL-1R (TIR)-containing adaptor molecules regulate these processes in vivo. In this model, DC maturation is impaired in TLR2(-/-), TLR4(-/-) and TIR domain-containing adapter-inducing IFN-beta (TRIF)(-/-) mice. In contrast, DC apoptosis is reduced only in TLR4(-/-) and TRIF(-/-) mice. As expected, DC apoptosis induced by the TLR4 ligand LPS is also abolished in these mice. Injection of the TLR9 ligand CpG-oligodeoxynucleotide (synthetic bacterial DNA) induces DC migration and maturation, but only modest DC apoptosis when compared with LPS and E. coli. Together, these results suggest that E. coli bacteremia directly impacts on DC maturation and survival in vivo through a TLR4-TRIF-dependent signaling pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport / deficiency
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / physiology*
  • Animals
  • Antigens, Differentiation* / biosynthesis
  • Antigens, Differentiation* / genetics
  • Apoptosis / immunology*
  • Cell Differentiation / immunology*
  • Cell Movement / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology*
  • Escherichia coli / growth & development
  • Escherichia coli / immunology*
  • Female
  • Injections, Intravenous
  • Interferon-beta / biosynthesis*
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Receptors, Interleukin-1 / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / microbiology
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Antigens, Differentiation
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • TICAM-1 protein, mouse
  • TIRAP protein, mouse
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Interferon-beta