Phosphatidylcholine-specific phospholipase C but not gamma interferon regulate gene expression and secretion of CC Chemokine Ligand-2 (CCL-2) by human astrocytes during infection by Toxoplasma gondii.
We have used human astrocytoma-derived cells to investigate the cellular responses of central nervous system cells to Toxoplasma gondii infection. At 24 h post inoculation, the secretion of CCL-2 (or Monocyte Chemotactic Protein-1) was augmented six-fold over the control. This secretion was down-regulated by D609, a specific inhibitor of phosphatidylcholine-dependent phospholipase C (PC-PLC), but not modulated by gamma interferon (IFN-gamma). Ribonuclease protection assay analyses showed significant down-regulation of CCL-2 mRNA production during infection by Toxoplasma gondii when cells were treated by D609. The mRNA levels of the seven other chemokines studied were not modified by D609. CCL-2 seems to contribute to the cell recruitment during human cerebral reactivation of Toxoplasma gondii. Cellular production of this CC chemokine during toxoplasmosis may be regulated by a PC-PLC-dependent pathway.
Durand
François
F
Interactions Cellulaires Parasite-Hôte, EA UJF 2940, Faculté de Médecine, Université J. Fourier, Grenoble, France. frdurand@chu-grenoble.fr
Brenier-Pinchart
Marie-Pierre
MP
Berger
Francois
F
Marche
Patrice N
PN
Grillot
Renée
R
Pelloux
Hervé
H
D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000469:parasitology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D009636:Norbornanes; D012333:RNA, Messenger / Q000032:analysis; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism*
D001952:Bridged-Ring Compounds; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D009636:Norbornanes; D012333:RNA, Messenger; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D007371:Interferon-gamma; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C