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.