Activation of neonatal and adult human macrophages by alpha, beta, and gamma interferons

Abstract

Increasing evidence suggests that gamma interferon (IFN-γ) is the major or sole factor in human lymphokines which activates blood monocyte-derived macrophages (MΦ) to inhibit or kill Toxoplasma gondii and certain other intracellular pathogens. In the current studies, we found that IFN-γ effectively activated tissue MΦ from adults (peritoneal MΦ) and from newborns (placental MΦ) as well as blood-derived MΦ from adults and from newborns to kill or to inhibit the replication of T. gondii. Results with purified and recombinant IFN-γ and with adult and newborn MΦ were similar. IFN-γ-treated MΦ were equally or more active against T. gondii than were freshly isolated monocytes and MΦ. Recombinant IFN-αA and IFN-β were less effective than IFN-γ. IFN-γ also inhibited survival and replication of T. gondii in WISH cells more effectively than did IFN-α and IFN-β. These findings are consistent with an important role for IFN-γ in the control of Toxoplasma infection and indicate that the anti-Toxoplasma activity of resting and IFN-γ-activated adult and neonatal MΦ is similar. The increased susceptibility of neonates to T. gondii is not due to a defect in MΦ effector function.