Wednesday, August 08, 2007

Rapid elimination of Toxo by IFNg-primed mouse macrophages is independent of CD40 signaling

Infect Immun. 2007 Aug 6; [Epub ahead of print]

Rapid elimination of Toxoplasma gondii by IFN{gamma}-primed mouse macrophages is independent of CD40 signaling

Zhao Y, Wilson D, Matthews S, Yap GS

Department of Molecular Microbiology and Immunology, Warren Alpert Medical School, Brown University, Providence, RI 02912.

Autophagy has been implicated in the intracellular destruction of Toxoplasma gondii by primed macrophages following IFNgamma activation of p47 GTPases. CD40 ligation has also been shown to trigger autophagic elimination of T. gondii independently of gamma interferon and p47 GTPases. Here we demonstrate that IFNgamma/p47 GTPase-dependent elimination of T. gondii by CPS-vaccine primed macrophages is independent of CD40/TNF signaling. Similar to WT controls, both CD40-deficient and TNFR1/2-deficient macrophages can efficiently eliminate invaded GFP-PTG and restrain their replication following priming. In contrast, IFNgammaR(-/-) macrophages neither clear the parasites nor repress their proliferation. Thus, CD40 and IFNgamma-induced pathogen elimination might represent two independent resistance pathways, the latter playing a primary role in anti-Toxoplasma immunity in mouse.

PMID: 17682046 [PubMed - as supplied by publisher]

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