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.
Department of Molecular Microbiology and Immunology, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA.
Yanlin
Y
Zhao
Douglas
D
Wilson
Suzanne
S
Matthews
George S
GS
Yap
D000818:Animals; D019013:CD40 Antigens / Q000172:deficiency / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000276:immunology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000172:deficiency / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology*
D019013:CD40 Antigens; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse; D007371:Interferon-gamma