title: Regulation of Toxoplasma gondii multiplication in BeWo trophoblast cells: cross-regulation of nitric oxide production and polyamine biosynthesis.
abstract: Materno-foetal transmission causes one of the most severe forms of infection with the protozoan parasite Toxoplasma gondii. Several studies have shown T. gondii in placental trophoblast cells, which form the barrier between maternal blood circulation and foetal tissue. Parasite multiplication in trophoblast cells is thus a critical step leading to infection of the foetus. Here, we show that multiplication of T. gondii tachyzoites was slow in BeWo trophoblast cells, compared with MRC-5 fibroblast cells. However, unlike MRC-5 cells, even combined stimulation with interferon-gamma and tumor necrosis factor-alpha did not reduce T. gondii replication in BeWo cells. This was associated with a lack of indoleamine-2,3-dioxygenase induction by these cytokines. Neither low availability of iron salts, nor an immunosuppressive action of cyclooxygenase-2 could be attributed to the low T. gondii multiplication rate in BeWo cells. However, treatment with the nitric oxide synthesis inhibitor N(G)-methyl-l-arginine and addition of ornithine enhanced the proliferation rate of the intracellular pathogen. Despite detection of inducible nitric oxide synthase-II mRNA in BeWo cells, nitric oxide production could not be detected during cell culture. Thus, inhibition of arginase activity by nitric oxide synthesis may be partially responsible for the lower multiplication rate in BeWo cells.
authors.affiliation: Institut de Parasitologie et de Pathologie Tropicale de Strasbourg, EA 1330 de la Faculté de Médecine: Interaction Cellulaire et Moléculaire Hôte-Parasite, Université Louis Pasteur, 3 rue Koeberlé, France. alexander.pfaff@medecine.u-strasbg.fr
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Pfaff
authors.forename: Odile
authors.initials: O
authors.lastname: Villard
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Klein
authors.forename: Marc
authors.initials: M
authors.lastname: Mousli
authors.forename: Ermanno
authors.initials: E
authors.lastname: Candolfi
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors; D005260:Female; D005347:Fibroblasts / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D018445:Infectious Disease Transmission, Vertical; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009952:Ornithine / Q000494:pharmacology; D010274:Parasitology / Q000379:methods; D011073:Polyamines / Q000378:metabolism*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000378:metabolism*; D012098:Reproduction; D014122:Toxoplasma / Q000502:physiology*; D014123:Toxoplasmosis / Q000378:metabolism / Q000635:transmission*; D014327:Trophoblasts / Q000378:metabolism / Q000469:parasitology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D011073:Polyamines; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D009952:Ornithine; D019001:Nitric Oxide Synthase; D001119:Arginase; D007213:Indomethacin