Role of CC chemokine receptor 1 and two of its ligands in human dengue infection. Three approaches under the Cuban situation |
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| Affiliation: | 1. Department of Microbiology, National University of Singapore, CeLS Building #03-05, 28 Medical Drive, 115597 Singapore, Singapore;2. Immunology Programme, National University of Singapore, CeLS Building #03-05, 28 Medical Drive, 115597 Singapore, Singapore;3. Inserm, U1019, F-59019 Lille, France;4. CNRS UMR8204, F-59019 Lille, France;5. Univ Lille Nord de France, F-59000 Lille, France;6. Institut Pasteur de Lille, F-59019 Lille, France;1. Department of Pediatric Urology, VU University Medical Centre, Amsterdam, The Netherlands;2. Pediatric Urology Centre, University Children''s Hospitals UMC Utrecht and Emma Children''s Hospital/AMC, Amsterdam, The Netherlands;3. Department of Pediatric Nephrology, VU University Medical Centre, Amsterdam, The Netherlands;1. Department of Internal Medicine, Saint Louis University, Doisy Research Center, 8th Floor, 1100 S. Grand Blvd., St. Louis, MO 63104, United States;2. Department of Molecular Microbiology and Immunology, Saint Louis University, Doisy Research Center, 7th Floor, 1100 S. Grand Blvd., St. Louis, MO 63104, United States;1. Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia;2. Department of Biochemistry–Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil;3. Department of Pathology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil;4. Department of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo, Brazil;5. Centro de Ciências Biológicas, Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Brazil;6. Departamento de Microbiologia e Parasitologia, Universidade Federal do Rio Grande do Norte, Natal, Brazil;7. Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Brazil;1. Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA;2. Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA |
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| Abstract: | Any of the four dengue serotypes can cause a severe disease, partly due to systemic inflammation orchestrated by mediators like cytokines and chemokines. We addressed the role of CCR1 and its ligands CCL3/MIP-1α and CCL5/RANTES in dengue infection using three different approaches: an ex vivo model exploring memory immune response in subjects with a well characterized dengue immune background, an in vivo study in patients with primary or secondary dengue infection, and an approach in fatal dengue. CCR1 and CCL3/MIP-1α gene expression showed differences after homotypic and heterotypic challenge according to dengue immune background of subjects, in correspondence with previous observations in Cuban dengue outbreaks. CCL5/RANTES gene expression was higher after homotypic challenge. CCR1 and CCL3/MIP-1α gene expression was higher in patients with secondary infection during critical days of the dengue disease, while the increase in RANTES expression started earlier than the observed for CCR1 and CCL3/MIP-1α. CCR1 and CCL3/MIP-1α gene expression was as high in brain as in spleen tissue from necropsy. Our results confirm the strong influence of previous immunity in subsequent dengue infections, and confer a possible pathogenic role to CCR1 and CCL3/MIP-1α in dengue disease and a possible protective role for CCL5/RANTES, probably through CCR5 interaction. |
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| Keywords: | Chemokines Gene expression Immunopathogenesis Dengue |
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