title: Virulent Toxoplasma gondii strain RH promotes T-cell-independent overproduction of proinflammatory cytokines IL12 and gamma-interferon.
abstract: The aim of this study was the analysis of the cytokine response in BALB/c mice infected with the highly virulent RH or the weakly virulent Beverley strains of Toxoplasma gondii. Analysis of cytokine messages showed increased expression of IL12, IFN-gamma and TNF-alpha, but not IL4 mRNAs in spleen cells after infection with the T. gondii strains RH and Beverley. High levels of circulating IL12 and IFN-gamma were detected in the serum of mice infected with strain RH, although TNF-alpha levels remained low. In contrast, the same cytokines were detected at only low levels in the serum of mice infected with the Beverley strain. Administration of antibody against IL12 or IFN-gamma significantly delayed time to death of mice infected with strain RH compared to controls. T-Cell-deficient as well as normal mice were equally infected by strain RH, suggesting that T lymphocytes do not contribute to the response. Depletion of natural killer cells from the splenocyte population abolished the in vitro production of IFN-gamma. Together, our data suggest that the virulent strain RH induces in BALB/c mice a type 1 cytokine pattern with T-cell-independent overproduction of IL12 and IFN-gamma that may be involved in the pathogenesis of this micro-organism.
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Nguyen
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bigaignon
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: D
authors.initials: D
authors.lastname: Markine-Goriaynoff
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: H
authors.initials: H
authors.lastname: Heremans
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Nguyen
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: G
authors.initials: G
authors.lastname: Warnier
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: M
authors.initials: M
authors.lastname: Delmee
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: M
authors.initials: M
authors.lastname: Warny
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Wolf
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: C
authors.initials: C
authors.lastname: Uyttenhove
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: J
authors.initials: J
authors.lastname: Van Snick
authors.affiliation: Microbiology Unit, Cliniques Universitaires Saint-Luc1 and Experimental Medicine Unit2, Christian de Duve Institute of Cellular Pathology, Catholic University of Louvain and Ludwig Institute for Cancer Research3, Brussels, Belgium 4Laboratory Immunobiol, REGA Institute, K. U. Leuven, Belgium 5Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 6Wyeth Inc., Cambridge, MA 02140, USA.
authors.forename: J-P
authors.initials: JP
authors.lastname: Coutelier
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014774:Virulence
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma