Toxoplasma gondii induces the secretion of monocyte chemotactic protein-1 in human fibroblasts, in vitro

Secretion of Monocyte Chemotactic Protein-1 (MCP-1) by fibroblasts infected with Toxoplasma gondii was studied in vitro. A significantly higher MCP-1 secretion was observed 24 h after infection by live tachyzoites. Analysis o f chemokine mRNA transcripts by RNase protection assay revealed that this M CP-1 secretion seems associated with increased MCP-1 mRNA expression. Howev er, these increased levels of MCP-1 secretion and expression were not obtai ned after stimulation by heat-killed tachyzoites or parasites pre-treated b y a specific inhibitor of phosphatidylcholine-specific phospholipase C (D60 9). Inhibition of parasite multiplication by pyrimethamine did not modify M CP-1 secretion. Thus, it appeared that the active penetration of T. gondii in cells was of major importance in the induction of MCP-1 secretion. None of the other chemokines studied by RNase protection assay (lymphotactin, RA NTES, IP-10, MIP-1 alpha, MIP-1 beta, IL-8, and I-309) were expressed after infection by live tachyzoites. We also found that MCP-1 secretion induced by live T. gondii is blocked by inhibitors of nuclear factor (NF)-kappa act ivation, ALLN and MG132. Such data indicate that NF-kappa B could be involv ed in T. gondii-induced MCP-1 production. MCP-1 secretion may contribute to the recruitment of monocytes and lymphocytes and thus participate in the c ontrol of T. gondii infection and in its pathogenesis.