Cutting edge: dendritic cells are essential for in vivo IL-12 production and development of resistance against Toxoplasma gondii infection in mice

J Immunol. 2006 Jul 1;177(1):31-5. doi: 10.4049/jimmunol.177.1.31.

Abstract

A powerful IFN-gamma response is triggered upon infection with the protozoan parasite, Toxoplasma gondii. Several cell populations, including dendritic cells (DCs), macrophages, and neutrophils, produce IL-12, a key cytokine for IFN-gamma induction. However, it is still unclear which of the above cell populations is its main source. Diphtheria toxin (DT) injection causes transient DC depletion in a transgenic mouse expressing Simian DT receptors under the control of the CD11c promoter, allowing us to investigate the role of DCs in IL-12 production. T. gondii-inoculated DT-treated and control groups were monitored for IL-12 levels and survival. We show in this study that DC depletion abolished IL-12 production and led to mortality. Furthermore, replenishment with wild-type, but not MyD88- or IL-12p35-deficient, DCs rescued IL-12 production, IFN-gamma-induction, and resistance to infection in DC-depleted mice. Taken together, the results presented in this study indicate that DCs constitute the major IL-12-producing cell population in vivo during T. gondii infection.

MeSH terms

  • Acute Disease
  • Adaptor Proteins, Signal Transducing / deficiency
  • Adaptor Proteins, Signal Transducing / genetics
  • Adoptive Transfer
  • Animals
  • Antigens, Protozoan / administration & dosage
  • Antigens, Protozoan / immunology
  • Cell Death / genetics
  • Cell Death / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / transplantation
  • Immunity, Innate / genetics
  • Immunosuppression Therapy
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / deficiency
  • Interleukin-12 / genetics
  • Interleukin-12 Subunit p35
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88
  • Protein Subunits / deficiency
  • Protein Subunits / genetics
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / transplantation
  • Toxoplasma / immunology*
  • Toxoplasmosis, Animal / genetics
  • Toxoplasmosis, Animal / mortality
  • Toxoplasmosis, Animal / pathology
  • Toxoplasmosis, Animal / prevention & control*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Protozoan
  • Interleukin-12 Subunit p35
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Protein Subunits
  • soluble tachyzoite antigen, Toxoplasma gondii
  • Interleukin-12