Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice
| Autor: | Helton C. Santiago, Joseph D. Weaver, Victoria Hoffman, Wuzhou Wan, Ana Paula M. P. Marino, Ester Roffê, Philip M. Murphy, Fernanda Fortes de Araujo |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Vasculitis 0301 basic medicine Pathology medicine.medical_specialty Necrosis Trypanosoma cruzi Immunology Parasitemia medicine.disease_cause Microbiology Autoimmunity Mice 03 medical and health sciences Immune system Necrotizing Vasculitis medicine Animals Paralysis Chagas Disease Lymphocytes RNA Messenger Muscle Skeletal Myositis biology medicine.disease biology.organism_classification Hindlimb Mice Inbred C57BL 030104 developmental biology Infectious Diseases Gene Expression Regulation Parasitology Tumor necrosis factor alpha Fungal and Parasitic Infections medicine.symptom |
| Zdroj: | Infection and Immunity. 84:1123-1136 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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