Toxoplasma gondii soluble antigen induces a subset of lipopolysaccharide-inducible genes and tyrosine phosphoproteins in peritoneal macrophages.

AUTOR(ES)

Li, Z Y

RESUMO

Previous studies have shown that macrophages play an important role in both the initiation of protective responses and the effector mechanism of immunity to Toxoplasma gondii. The purpose of this investigation was to characterize the responses of macrophages to a soluble antigen extract of T. gondii tachyzoites (STAg) in comparison with a prototypic macrophage-activating agent, lipopolysaccharide (LPS), and to determine whether STAg-induced signaling requires a functional Lps gene. Toward this end, tumor necrosis factor (TNF) secretion, a panel of six LPS-inducible genes, and protein tyrosine phosphorylation were examined to gain insights into macrophage responses to STAg. STAg stimulated both C3H/OuJ (Lpsn) and C3H/HeJ (Lpsd) macrophages to secrete bioactive TNF-alpha and to express a subset of LPS-inducible genes (encoding TNF-alpha, TNF receptor 2, and interleukin-1 beta). In contrast to LPS, STAg failed to stimulate Lpsn or Lpsd macrophages to express genes encoding IP-10, D3, or D8. STAg also induced a pattern of tyrosine phosphorylation identical to that induced by LPS; mitogen-activated protein kinase 47-kDa and 43-kDa isoforms and a 41-kDa protein of undetermined identity were inducibly phosphorylated. The ability of STAg to induce TNF-alpha, encoded by a subset of LPS-inducible genes, and tyrosine phosphoproteins was not affected by LPS inhibitors, confirming that the macrophage response to the parasite extract could not be attributed to LPS contamination. We propose that STAg, while differing from LPS in the pattern of macrophage genes induced, may share with LPS two signaling pathways that are intact in Lpsd macrophages.

Documentos Relacionados

• Mechanisms of killing of Toxoplasma gondii by rat peritoneal macrophages.
• Lipopolysaccharide-inducible and salicylate-sensitive nuclear factor(s) on human tumor necrosis factor alpha promoter.
• C/EBP-related protein 2 confers lipopolysaccharide-inducible expression of interleukin 6 and monocyte chemoattractant protein 1 to a lymphoblastic cell line.
• Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages.
• Beta interferon inhibits Toxoplasma gondii growth in human monocyte-derived macrophages.