In vivo role of IFN-gamma produced by antigen-presenting cells in early host defense against intracellular pathogens.
Antigen-presenting cells (APC), including dendritic cells and macrophages, produce a large amount of interferon (IFN)-gamma, a crucial cytokine for the control of infectious diseases. To elucidate the role of IFN-gamma from APC in vivo, we employed cytokine receptor common gamma subunit (gamma c) and recombination-activating gene (Rag)-2 double-knockout (gamma c(-/-(y))-Rag-2(-/-)) mice, which are severely impaired in IFN-gamma production and are extremely susceptible to infection of intracellular pathogens including Listeria monocytogenes and Toxoplasma gondii. Adoptive transfer of IFN-gamma-producing APC increased levels of serum IFN-gamma and the resistance to Listeria. Although depletion of NK cells from Rag-2(-/-) mice slightly increased the susceptibility to bacterial infection, they are substantially more resistant than gamma c(-/-(y))-Rag-2(-/-) mice, which are also devoid of all lymphoid cells. These results demonstrate that the APC-derived IFN-gamma contributes to the control of infectious agents in vivo.
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004198:Disease Susceptibility; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D007371:Interferon-gamma