Paralysis of dendritic cell IL-12 production by microbial products prevents infection-induced immunopathology

Immunity. 1999 Nov;11(5):637-47. doi: 10.1016/s1074-7613(00)80138-7.


Interleukin-12 plays a major role in immunity to intracellular pathogens by governing the development of IFNgamma-dependent host resistance. Nevertheless, unregulated IL-12 synthesis can lead to immunopathology, an outcome prevented by the concurrent expression of interleukin-10. Dendritic cells (DC) are an important source of the initial IL-12 stimulated by microbial agents. Here, we show that, following systemic triggering, DC can no longer be restimulated to produce IL-12 in vivo while continuing to respond in vitro. When infected with Toxoplasma gondii during this refractory state, mice mount impaired acute IFNgamma responses and, in the case of IL-10-deficient animals, are protected from cytokine-induced mortality. These findings demonstrate a previously unrecognized form of immunologic paralysis involving DC that can protect from infection-induced immunopathology.

MeSH terms

  • Animals
  • Antigens, Protozoan / immunology*
  • Antigens, Protozoan / pharmacology
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Host-Parasite Interactions
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / deficiency
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / deficiency
  • Interleukin-12 / genetics
  • Interleukin-12 / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Models, Immunological*
  • Spleen / immunology
  • Toxoplasma / immunology*
  • Toxoplasmosis, Animal / complications
  • Toxoplasmosis, Animal / immunology*
  • Toxoplasmosis, Animal / pathology


  • Antigens, Protozoan
  • soluble tachyzoite antigen, Toxoplasma gondii
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma