Rapid elimination of Toxoplasma gondii by gamma interferon-primed mouse macrophages is independent of CD40 signaling.

Autophagy has been implicated in the intracellular destruction of Toxoplasma gondii by primed macrophages following gamma interferon (IFN-gamma) activation of p47 GTPases. CD40 ligation has also been shown to trigger autophagic elimination of T. gondii independent of IFN-gamma and p47 GTPases. Here we demonstrate that IFN-gamma/p47 GTPase-dependent elimination of T. gondii by strain CPS vaccine-primed macrophages is independent of CD40/tumor necrosis factor signaling. Similar to wild-type controls, both CD40-deficient and tumor necrosis factor receptor 1/2 (TNFR1/2)-deficient macrophages can efficiently eliminate invaded strain GFP-PTG and restrain its replication following priming. In contrast, macrophages from mice lacking the IFN-gamma receptor gene neither clear the parasites nor repress their proliferation. Thus, CD40 and IFN-gamma-induced pathogen elimination might represent two independent resistance pathways, the latter of which plays a primary role in anti-Toxoplasma immunity in mice.