Beneficial effects of acetylsalicylic acid (aspirin) on the actions of extracellular vesicles shed by Trypanosoma cruzi in macrophages |
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| Institution: | 1. Laboratory of Experimental Immunopathology, Department of Pathological Sciences, State University of Londrina, Londrina, Brazil;2. Postgraduate Program of Microbiology, Department of Microbiology, UEL, Londrina, Paraná, Brazil;1. Facultad de Ciencias del Mar y de Recursos Naturales, Universidad de Valparaíso, Avenida Borgoño 16344, Viña del Mar, Chile;2. Centro de Observación Marino para Estudios de Riesgo del Ambiente (Costa-R), Universidad de Valparaíso, Valparaíso, Chile;3. Research Center Dynamics of High Latitude Marine Ecosystems (Fondap- IDEAL), Universidad Austral de Chile, Valdivia, Chile;4. Laboratorio de Ecología de Macroalgas Antárticas y Sub antárticas, Universidad de Magallanes, Punta Arenas, Chile;1. Department of Parasitology, Faculty of Veterinary Medicine, Cairo University, Egypt;2. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt;1. Department of Tropical Medicine and Parasitology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;2. Department of Parasitology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0374, Japan;3. Center for Laboratory Animal Science, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan;4. Department of Parasitology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan;5. Laboratory of Proteomics and Biomolecular Science, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;6. Laboratory of Molecular Biology, Graduate School of Environmental Health Sciences, Azabu University, 1-17-71 Fuchinobe Chuou-ku, Sagamihara 252-5201, Japan;1. Department Otorhinolaryngology-Head & Neck Surgery, Himeji St. Mary''s Hospital, Himeji, Japan;2. Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;3. Department of Otorhinolaryngology, International University of Health and Welfare School of Medicine, Narita, Japan |
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| Abstract: | Trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease, shed extracellular vesicles (EVs) that promote the susceptibility of host cells to infection. During T. cruzi infection, the immune response of the host is important for controlling parasitism, which is necessary for survival. Macrophages produce inflammatory mediators, such as eicosanoids and nitric oxide (NO), with trypanocidal effects that control the parasite load in the early stages of the disease. In this study, we evaluated the contribution of host cyclooxygenase (COX) to the actions of EVs shed by T. cruzi strain Y (EVs-Y) in infected macrophages. RAW 264.7 macrophages exposed to EVs-Y and then infected with trypomastigote forms of T. cruzi produced less NO, and an increased number of trypomastigote forms were internalized in the cell compared to the controls, indicating that the effects exerted by EVs-Y favor the parasite. Interestingly, when macrophages were pretreated with acetylsalicylic acid, a dual COX inhibitor, before exposure to EVs-Y and subsequent infection with trypomastigote forms, there was an increase in NO production and a decrease in trypomastigote uptake compared to the controls. These results suggest that EVs-Y modulates the macrophage response in favor of T. cruzi and indicate a role for COX in the effects of EVs. |
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