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Role of invariant NKT cells in lipopolysaccharide-induced lethal shock during encephalomyocarditis virus infection
Affiliation:1. Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan;2. Department of Medical Technology, Kansai University of Health Sciences, 2-11-1 Wakaba, Kumatori, Osaka 590-0482, Japan;3. Division of Animal Experiment, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan;4. Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan;1. Department of Paediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy;2. Department of Maternal and Children’s Health, Obstetrics and Gynecology Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy;3. Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Italy;4. Department of Maternal and Children’s Health, Neonatal Intensive Care Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy;1. Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal;2. CIISA, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. Universidade Técnica, 1300-477 Lisboa, Portugal;3. CEDOC, Chronic Diseases Research Center, Immunology, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires de Pátria, 1169-056 Lisboa, Portugal;4. Instituto de Investigação e Inovação em Saúde and Instituto de Biologia Molecular e Celular (IBMC), Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal;1. Environmental and Experimental Pathology, Paulista University (UNIP), Rua Dr. Bacelar 1212, 4th Floor, 04026-002, São Paulo, SP, Brazil;2. Microbiology, Immunology and Parasitology Department, Federal University, Rua Sena Madureira 1500, 04021-001, São Paulo, SP, Brazil;3. Physiopathology Department, Butantan Institute, Rua Vital Brasil 1500, 05503-900, São Paulo, SP, Brazil;1. Center for Innovation Competence, Humoral Immune Reactions in Cardiovascular Diseases, University Medicine Greifswald, 17489 Greifswald, Germany;2. Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, 17475 Greifswald, Germany;1. Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose Street Rm MS409, Lexington, KY 40536, USA;2. Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone Street Suite 292, Lexington, KY 40536, USA;3. Department of Internal Medicine, University of Kentucky College of Medicine, 900 S. Limestone Street Suite 303, Lexington, KY 40536, USA
Abstract:Viral infections can give rise to secondary bacterial infections. In the present study, we examined the role of invariant natural killer T (iNKT) cells in lipopolysaccharide (LPS)-induced lethal shock during encephalomyocarditis virus (EMCV) infection. Wild-type (WT) mice and Jα18 gene knockout (Jα18 KO) mice were inoculated with EMCV, 5 days prior to challenging with LPS. The survival rate of Jα18 KO mice subjected to EMCV and LPS was significantly higher than that of WT mice. TNF-α and nitric oxide (NO) production were increased in WT mice, than that in Jα18 KO mice, after the administration of EMCV and LPS. EMCV infection increased the number of iNKT cells and IFN-γ production by iNKT cells in WT mice. Moreover, EMCV infection enhanced the expression of Toll-like receptor 4 (TLR4) in the lung and spleen. IFN-γ also increased the expression of TLR4 in splenocytes. These findings indicated that EMCV infection activated iNKT cells, and IFN-γ secreted from the iNKT cells up-regulated the expression of TLR4 in various tissues. As a result, EMCV-infected mice were susceptible to LPS and easily developed the lethal shock. In conclusion, iNKT cells were involved in the development of LPS-induced lethal shock during EMCV infection.
Keywords:Endotoxin shock  Natural killer T cell  Encephalomyocarditis virus  Toll-like receptor 4  Inducible nitric oxide synthase
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