title: Toxoplasma gondii infection inhibits Th17-mediated spontaneous development of arthritis in interleukin-1 receptor antagonist-deficient mice.
abstract: Interleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection with Toxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed in T. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c(+) cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c(+) cells also produced IL-10, IL-1β, and IL-6, CD4(+) T cells from T. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of the T. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.
authors.affiliation: Department of Infection and Host Defense, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Washino
authors.forename: Masataka
authors.initials: M
authors.lastname: Moroda
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Fumie
authors.initials: F
authors.lastname: Aosai
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology*; D039521:CD11c Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D056660:Hereditary Autoinflammatory Diseases / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D053590:Interleukin 1 Receptor Antagonist Protein / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma