Decreased Resistance of TNF Receptor p55- and p75-Deficient Mice to Chronic Toxoplasmosis Despite Normal Activation of Inducible Nitric Oxide Synthase In Vivo

摘要: The importance of TNF-α in host defense to the intracellular parasite, Toxoplasma gondii , was investigated mice lacking both p55 and p75 receptors for this cytokine. Upon i.p. infection with avirulent ME49 strain, knockout were capable limiting acute infection, but succumbed within 3 4 wk a fulminant necrotizing encephalitis. Receptor-deficient harbored higher cyst burdens exhibited uncontrolled tachyzoite replication brain. lack TNF did not adversely affect development type 1 IFN-γ response. In vitro studies peritoneal macrophages stimulated tachyzoites indicated that under concentrations IFN-γ, nitric oxide-mediated toxoplasmastatic activity is dependent. However, requirement overcome by increasing dose IFN-γ. Furthermore, ex vivo demonstrated inducible oxide synthase induction cavity brain unimpaired receptor-deficient mice. Thus, TNF-dependent immune control T. expansion involves an effector function distinct from activation.