TOXOPLASMA-GONDII SOLUBLE-ANTIGEN INDUCES A SUBSET OF LIPOPOLYSACCHARIDE-INDUCIBLE GENES AND TYROSINE PHOSPHOPROTEINS IN PERITONEAL-MACROPHAGES

Previous studies have shown that macrophages play an important role in both the initiation of protective responses and the effector mechanis m 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 prototypi c macrophage-activating agent, lipopolysaccharide (LPS), and to determ ine whether STAg-induced signaling requires a functional Lps gene. Tow ard this end, tumor necrosis factor (TNF) secretion, a panel of six LP S-inducible genes, and protein tyrosine phosphorylation were examined to gain insights into macrophage responses to STAg. STAg stimulated bo th C3H/OuJ (Lps(n)) and C3H/HeJ (Lps(d)) macrophages to secrete bioact ive TNF-alpha and to express a subset of LPS-inducible genes (encoding TNF-alpha, TNF receptor 2, and interleukin-1 beta). In contrast to LP S, STAg failed to stimulate Lps(n) or Lps(d) macrophages to express ge nes encoding IF-10, D3, or D8. STAg also induced a pattern of tyrosine phosphorylation identical to that induced by LPS; mitogen-activated p rotein kinase 47-kDa and 43-kDa isoforms and a 41-kDa protein of undet ermined identity were inducibly phosphorylated. The ability of STAg to induce TNF-alpha, encoded by a subset of LPS-inducible genes, and tyr osine phosphoproteins was not affected by LPS inhibitors, confirming t hat the macrophage response to the parasite extract could not be attri buted to LPS contamination. We Propose that STAg, while differing from LPS in the pattern of macrophage genes induced, may share with LPS tw o signaling pathways that are intact in Lds(d) macrophages.