Deficiency in indoleamine-2, 3-dioxygenase induces upregulation of guanylate binding protein 1 and inducible nitric oxide synthase expression in the brain during cerebral infection with Toxoplasma gondii in genetically resistant BALB/c mice but not in genetically susceptible C57BL/6 mice |
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Affiliation: | 1. Departamento de Microbiología e Inmunología, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta Nacional 36, Km 601, X5804ZAB Río Cuarto, Córdoba, Argentina;2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina;1. Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran;2. Health Sciences Unit, Faculty of Social Sciences, Tampere University, Tampere, Finland;3. HPGC Research Group, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran;4. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, USA;5. Department of Epidemiology & Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;6. Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Tehran, Iran;7. Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran;1. Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;2. Programa de Pós-Graduação em Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;3. Centro de Referência Nacional em Hanseníase e Dermatologia Sanitária, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil;4. Secretaria de Estado da Saúde de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;5. Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;6. Programa de Pós-Graduação em Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil;1. Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa, Paraíba, 58051-900, Brazil;2. Post-graduation Program in Biotechnology, Center of Biotechnology of Federal University of Paraíba, João Pessoa, Paraíba, 58051-900, Brazil;3. Molecular Biology of Cancer and Infectious Diseases Laboratory of Post-Graduation Program on Parasite Biology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, 58078-970, Brazil;4. Research Institute for Drugs and Medicines, Federal University of Paraiba, João Pessoa, Paraíba, 58051-900, Brazil;5. Department of Infectious Disease, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, London, W12 0NN, United Kingdom;6. Department of Immunology and Inflammation, Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, London, W12 0NN, United Kingdom;1. Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China;2. Hospital of Stomatology, Jilin University, Changchun 130021, China;3. Shandong Jinzhuji Pharmaceuticals Co. Ltd., Jinan 271100, Shandong, China |
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Abstract: | We examined the roles of indoleamine-2, 3-dioxygenase 1 (IDO1) in controlling cerebral Toxoplasma gondii infection in both genetically resistant and susceptible strains of mice. In susceptible C57BL/6 mice, IDO expression was immunohistochemically detected only in a minority (22.5%) of tachyzoite-infected cells in their brains during the later stage of infection. When C57BL-6-background IDO1-deficient (IDO1?/?) mice were infected, their cerebral tachyzoite burden was equivalent to those of wild-type (WT) animals. In contrast, in resistant BALB/c mice, IDO expression was detected in a majority (84.0%) of tachyzoite-infected cerebral cells. However, tachyzoite burden in BALB/c-background IDO1?/? mice remained as low as that of WT mice, which was 78 times less than those of C57BL/6 mice. Of interest, IDO1?/? mice of only resistant BALB/c-background had markedly greater cerebral expressions of two other IFN-γ-mediated effector molecules, guanylate binding protein 1 (Gbp1) and nitric oxide synthase 2 (NOS2), than their WT mice. Therefore, it would be possible that IDO1 deficiency was effectively compensated by the upregulated expression of Gbp1 and NOS2 to control cerebral tachyzoite growth in genetically resistant BALB/c mice, whereas IDO1 did not significantly contribute to controlling cerebral tachyzoite growth in genetically susceptible C57BL/6 mice because of its suppressed expression in infected cells. |
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Keywords: | Genetic resistance Protective immunity Indoleamine-2,3-dioxigenase Guanylate binding protein 1 Nitric oxide synthase 2 |
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