In vivo role of IFN-γ 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)-γ, a crucial cytokine for the control of infectious diseases. To elucidate the role of IFN-γ from APC in vivo, we employed cytokine receptor common γ subunit (γc) and recombination-activating gene (Rag -2 double-knockout (γc^-/-(y)-Rag-2^-/-) mice, which are severely impaired in IFN-γ production and are extremely susceptible to infection of intracellular pathogens including Listeria monocytogenes and Toxoplasma gondii. Adoptive transfer of IFN-γ-producing APC increased levels of serum IFN-γ 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 γc^-/-(y)-Rag-2^-/- mice, which are also devoid of all lymphoid cells. These results demonstrate that the APC-derived IFN-γ contributes to the control of infectious agents in vivo.