Toxoplasma gondii Triggers Granulocyte-Dependent Cytokine-Mediated Lethal Shock in d-Galactosamine-Sensitized Mice

摘要: To investigate the capacity of Toxoplasma gondii to induce cytokine-mediated toxicity, we employed a murine model lethal shock in which hypersensitivity microbial toxins is induced by d-galactosamine (d-Gal). Animals injected with d-Gal and tachyzoite lysate died within 12 24 h, whereas administration or alone was nonlethal. Analyses plasma cytokines revealed peaks tumor necrosis factor (TNF) alpha interleukin-12 (IL-12) 1 3 5 h after injection, respectively, gradually rising levels gamma interferon (IFN-γ) continuing until death. Nitric oxide (NO) serum paralleled IFN-γ production. Transaminase assays elevated liver-associated enzymes sera lethally mice, indicating severe hepatic damage. Depletion IL-12, TNF, IFN-γ, NO rescued mice from effect antigen (Ag) d-Gal. T-cell-deficient animals remained sensitive lysate, suggesting that T lymphocytes do not contribute response. Nevertheless, monoclonal antibody (MAb)-mediated granulocyte depletion completely abrogated d-Gal- Ag-induced mortality accompanying liver pathology. Finally, acutely infected T. displayed highly enzyme immediately prior death, anti-TNF MAb prolonged survival approximately h. Our results demonstrate induces inflammatory cytokine d-Gal-sensitized suggest similar pathology may manifestations acute toxoplasmosis.