Rapid Elimination ofToxoplasma gondiiby Gamma Interferon-Primed Mouse Macrophages Is Independent of CD40 Signaling

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Abstract
Autophagy has been implicated in the intracellular destruction ofToxoplasma gondiiby primed macrophages following gamma interferon (IFN-γ) activation of p47 GTPases. CD40 ligation has also been shown to trigger autophagic elimination ofT. gondiiindependent of IFN-γ and p47 GTPases. Here we demonstrate that IFN-γ/p47 GTPase-dependent elimination ofT. gondiiby 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-γ receptor gene neither clear the parasites nor repress their proliferation. Thus, CD40 and IFN-γ-induced pathogen elimination might represent two independent resistance pathways, the latter of which plays a primary role in anti-Toxoplasmaimmunity in mice.

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