Regulatory T Cells Promote Myositis and Muscle Damage in Toxoplasma Gondii Infection

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2016 Nov 30

PMID 27895180

Citations 30

Authors

Richard M Jin

Sarah J Blair

Jordan Warunek

Reid R Heffner

Ira J Blader

Elizabeth A Wohlfert

Affiliations

Soon will be listed here.

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.

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