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 of chemokine mRNA transcripts by RNase protection assay revealed that this MCP-1 secretion seems associated with increased MCP-1 mRNA expression. However, these increased levels of MCP-1 secretion and expression were not obtained after stimulation by heat-killed tachyzoites or parasites pre-treated by a specific inhibitor of phosphatidylcholine-specific phospholipase C (D609). Inhibition of parasite multiplication by pyrimethamine did not modify MCP-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, RANTES, IP-10, MIP-1alpha, MIP-1beta, 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)-kappaB activation, ALLN and MG132. Such data indicate that NF-kappaB could be involved in T. gondii-induced MCP-1 production. MCP-1 secretion may contribute to the recruitment of monocytes and lymphocytes and thus participate in the control of T. gondii infection and in its pathogenesis.
Brenier-Pinchart
M P
MP
Département de Parasitologie-Mycologie Médicale et Moléculaire (RHAP- DP3M) UPRES-A CNRS 5082, Faculté de Médecine, Université Joseph Fourier, Grenoble 1, La Tronche, France.
Pelloux
H
H
Simon
J
J
Ricard
J
J
Bosson
J L
JL
Ambroise-Thomas
P
P
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000469:parasitology* / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009636:Norbornanes; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011739:Pyrimethamine / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013871:Thiones / Q000494:pharmacology; D013997:Time Factors; D014122:Toxoplasma / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000981:Antiprotozoal Agents; D001952:Bridged-Ring Compounds; D018932:Chemokine CCL2; D018925:Chemokines; D004791:Enzyme Inhibitors; D007976:Leupeptins; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C066229:prolinedithiocarbamate; C046498:tricyclodecane-9-yl-xanthogenate; D011392:Proline; D010738:Type C Phospholipases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D011739:Pyrimethamine