title: Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice.
abstract: Infectious agents are often considered potential triggers of chronic inflammatory disease, including autoimmunity; however, direct evidence is usually lacking. Here we show that following control of acute infection of mice with the myotropic Colombiana strain of Trypanosoma cruzi, parasites persisted in tissue at low levels associated with development of systemic necrotizing vasculitis. Lesions occurred in many but not all organs and tissues, with skeletal muscle arteries being the most severely affected, and were associated with myositis, atrophy, paresis/paralysis, and death. Histopathology showed fibrinoid vascular necrosis, rare amastigote nests within skeletal muscle myocytes, and massive leukocyte infiltrates composed mainly of inflammatory monocytes, F4/80(+)macrophages, and T. cruzi tetramer-specific CD8(+) T lymphocytes capable of producing gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) but not interleukin-17 (IL-17). T. cruzi-specific IgG was detected in sera from infected mice, but antibody deposits and neutrophilic inflammation were not features of the lesions. Thus,T. cruzi infection of mice may be a specific infectious trigger of paralyzing systemic necrotizing vasculitis most severely affecting skeletal muscle, driven by pathogen-specific type I immune responses.
authors: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: Ester
authors: E
authors: Roffê
authors: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: Ana Paula M P
authors: APMP
authors: Marino
authors: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: Joseph
authors: J
authors: Weaver
authors: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors: Wuzhou
authors: W
authors: Wan
authors: Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors: Fernanda F
authors: FF
authors: de Araújo
authors: Division of Veterinary Resources, Office of Research Services, Office of the Director, NIH, Bethesda, Maryland, USA.
authors: Victoria
authors: V
authors: Hoffman
authors: Helminth Immunology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors: Helton C
authors: HC
authors: Santiago
authors: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA pmm@nih.gov.
authors: Philip M
authors: PM
authors: Murphy
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D006614:Hindlimb / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D010243:Paralysis / Q000469:parasitology* / Q000473:pathology; D018512:Parasitemia; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014349:Trypanosoma cruzi; D014657:Vasculitis / Q000276:immunology / Q000469:parasitology* / Q000473:pathology*
chemical_list: D012333:RNA, Messenger