title: Regulatory T Cells Promote Myositis and Muscle Damage in Toxoplasma gondii Infection.
abstract: The coordination of macrophage polarization is essential for the robust regenerative potential of skeletal muscle. Repair begins with a phase mediated by inflammatory monocytes (IM) and proinflammatory macrophages (M1), followed by polarization to a proregenerative macrophage (M2) phenotype. Recently, regulatory T cells (Tregs) were described as necessary for this M1 to M2 transition. We report that chronic infection with the protozoan parasite Toxoplasma gondii causes a nonresolving Th1 myositis with prolonged tissue damage associated with persistent M1 accumulation. Surprisingly, Treg ablation during chronic infection rescues macrophage homeostasis and skeletal muscle fiber regeneration, showing that Tregs can directly contribute to muscle damage. This study provides evidence that the tissue environment established by the parasite could lead to a paradoxical pathogenic role for Tregs. As such, these findings should be considered when tailoring therapies directed at Tregs in inflammatory settings.
authors.affiliation: Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214; and.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Jin
authors.affiliation: Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214; and.
authors.forename: Sarah J
authors.identifier: 0000-0002-4837-6424
authors.initials: SJ
authors.lastname: Blair
authors.affiliation: Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214; and.
authors.forename: Jordan
authors.initials: J
authors.lastname: Warunek
authors.affiliation: Department of Pathology and Anatomical Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214.
authors.forename: Reid R
authors.initials: RR
authors.lastname: Heffner
authors.affiliation: Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214; and.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Blader
authors.affiliation: Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214; and wohlfert@buffalo.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wohlfert
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009220:Myositis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000473:pathology