Differential induction of interleukin-10 and interleukin-12 in dendritic cells by microbial toll-like receptor activators and skewing of T-cell cytokine profiles

Infect Immun. 2003 Jun;71(6):3337-42. doi: 10.1128/IAI.71.6.3337-3342.2003.

Abstract

Dendritic cells (DCs) discriminate different microbial pathogens and induce T-cell responses of appropriate effector phenotypes accordingly. Microbial recognition and differentiation are mediated in part by pattern recognition receptors such as Toll-like receptors (TLRs), whereas the development of T-cell effector functions is critically dependent on DC-derived cytokines such as interleukin-12 (IL-12) and IL-10. However, it is not entirely clear to what extent various microbial TLR activators could induce different functional states of DCs that favor different T-cell effector phenotypes. Toward a better understanding of this issue, we examined IL-10 and IL-12 production and T-cell-polarizing potentials of murine bone marrow-derived DCs after stimulation by three microbial TLR activators, namely, lipopolysaccharide (LPS), peptidoglycan (PGN), and zymosan. We found that the three stimuli induced drastically different profiles of IL-10 and IL-12 production in DCs. Further, these stimuli differentially conditioned CD40-dependent IL-10 and IL-12 production by DCs. Finally, LPS-, PGN-, and zymosan-stimulated DCs primed distinct T-cell cytokine profiles. Our results support the notion that microbe-specific information sensed through different TLRs by DCs is linked to differential Th priming through DC-derived cytokines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD40 Antigens / physiology
  • Cytokines / biosynthesis*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Female
  • Interleukin-10 / biosynthesis*
  • Interleukin-12 / biosynthesis
  • Lipopolysaccharides / pharmacology*
  • Membrane Glycoproteins / physiology*
  • Mice
  • Peptidoglycan / pharmacology*
  • Receptors, Cell Surface / physiology*
  • T-Lymphocytes / immunology*
  • Toll-Like Receptors
  • Zymosan / pharmacology*

Substances

  • CD40 Antigens
  • Cytokines
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Peptidoglycan
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Interleukin-10
  • Interleukin-12
  • Zymosan