title: In vitro infection of human nervous cells by two strains of Toxoplasma gondii: a kinetic analysis of immune mediators and parasite multiplication.
abstract: The severity of toxoplasmic infection depends mainly on the immune status of the host, but also on the Toxoplasma gondii strains, which differ by their virulence profile. The relationship between the human host and T. gondii has not yet been elucidated because few studies have been conducted on human models. The immune mechanisms involved in the persistence of T. gondii in the brains of immunocompetent subjects and during the reactivation of latent infections are still unclear. In this study, we analyzed the kinetics of immune mediators in human nervous cells in vitro, infected with two strains of T. gondii. Human neuroblast cell line (SH SY5Y), microglial (CMH5) and endothelial cells (Hbmec) were infected separately by RH (type I) or PRU (type II) strains for 8 h, 14 h, 24 h and 48 h (ratio 1 cell: 2 tachyzoites). Pro-inflammatory protein expression was different between the two strains and among different human nervous cells. The cytokines IL-6, IL-8 and the chemokines MCP-1 and GROα, and SERPIN E1 were significantly increased in CMH5 and SH SY5Y at 24 h pi. At this point of infection, the parasite burden declined in microglial cells and neurons, but remained high in endothelial cells. This differential effect on the early parasite multiplication may be correlated with a higher production of immune mediators by neurons and microglial cells compared to endothelial cells. Regarding strain differences, PRU strain, but not RH strain, stimulates all cells to produce pro-inflammatory growth factors, G-CSF and GM-CSF. These proteins could increase the inflammatory effect of this type II strain. These results suggest that the different protein expression profiles depend on the parasitic strain and on the human nervous cell type, and that this could be at the origin of diverse brain lesions caused by T. gondii.
authors.affiliation: National Institute of Health and Medical Research 1094, Tropical Neuroepidemiology Institute, Limoges, France; University of Limoges, National Center for Scientific Research France 3503 Institute of Genomic, Environment, Immunity, Health and Therapy, Limoges, France.
authors.forename: Nour
authors.initials: N
authors.lastname: Mammari
authors.affiliation: National Institute of Health and Medical Research 1094, Tropical Neuroepidemiology Institute, Limoges, France; University of Limoges, National Center for Scientific Research France 3503 Institute of Genomic, Environment, Immunity, Health and Therapy, Limoges, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vignoles
authors.affiliation: National Center for Scientific Research France 7276, France 3503 Institute of Genomic, Environment, Immunity, Health and Therapy, University of Limoges, Faculty of Pharmacy, Limoges, France.
authors.forename: Mohamad Adnan
authors.initials: MA
authors.lastname: Halabi
authors.affiliation: National Institute of Health and Medical Research 1094, Tropical Neuroepidemiology Institute, Limoges, France; University of Limoges, National Center for Scientific Research France 3503 Institute of Genomic, Environment, Immunity, Health and Therapy, Limoges, France; Universitary Hospital, Department of Parasitology, Biological Resource Centre for Toxoplasma, Limoges, France.
authors.forename: Marie Laure
authors.initials: ML
authors.lastname: Darde
authors.affiliation: National Institute of Health and Medical Research 1094, Tropical Neuroepidemiology Institute, Limoges, France; University of Limoges, National Center for Scientific Research France 3503 Institute of Genomic, Environment, Immunity, Health and Therapy, Limoges, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Courtioux
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D007700:Kinetics; D051379:Mice; D009420:Nervous System / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014122:Toxoplasma / Q000254:growth & development*
chemical_list: D017931:DNA Primers