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IFN-γ production depends on IL-12 and IL-18 combined action and mediates host resistance to dengue virus infection in a nitric oxide-dependent manner
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نویسنده
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fagundes c.t. ,costa v.v. ,cisalpino d. ,amaral f.a. ,souza p.r.s. ,souza r.s. ,ryffel b. ,vieira l.q. ,silva t.a. ,atrasheuskaya a. ,ignatyev g. ,sousa l.p. ,souza d.g. ,teixeira m.m.
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منبع
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plos neglected tropical diseases - 2011 - دوره : 5 - شماره : 12
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چکیده
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Dengue is a mosquito-borne disease caused by one of four serotypes of dengue virus (denv-1-4). severe dengue infection in humans is characterized by thrombocytopenia,increased vascular permeability,hemorrhage and shock. however,there is little information about host response to denv infection. here,mechanisms accounting for ifn-γ production and effector function during dengue disease were investigated in a murine model of denv-2 infection. ifn-γ expression was greatly increased after infection of mice and its production was preceded by increase in il-12 and il-18 levels. in ifn-γ -/- mice,denv-2-associated lethality,viral loads,thrombocytopenia,hemoconcentration,and liver injury were enhanced,when compared with wild type-infected mice. il-12p40 -/- and il-18 -/- infected-mice showed decreased ifn-γ production,which was accompanied by increased disease severity,higher viral loads and enhanced lethality. blockade of il-18 in infected il-12p40 -/- mice resulted in complete inhibition of ifn-γ production,greater denv-2 replication,and enhanced disease manifestation,resembling the response seen in denv-2-infected ifn-γ -/- mice. reduced ifn-γ production was associated with diminished nitric oxide-synthase 2 (nos2) expression and nos2 -/- mice had elevated lethality,more severe disease evolution and increased viral load after denv-2 infection. therefore,il-12/il-18-induced ifn-γ production and consequent nos2 induction are of major importance to host resistance against denv infection. © 2011 fagundes et al. this is an open-access article distributed under the terms of the creative commons attribution license,which permits unrestricted use,distribution,and reproduction in any medium,provided the original author and source are credited.
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آدرس
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immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departmento de microbiologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departmento de microbiologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departmento de microbiologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departmento de microbiologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departmento de microbiologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departmento de microbiologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, molecular immunology and embryology umr6218,cnrs,orleans, France, departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, departmento de patologia oral,faculdade de odontologia,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, laboratory of immunology safety,state research center of virology and biotechnology vector,koltsovo,novosibirsk region, Russian Federation, state institute of standardizing and control by name of tarasevich,moscow,moscow province, Russian Federation, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departamento de análises clínicas e toxicológicas,faculdade de farmácia,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais,brazil,departmento de microbiologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil, immunopharmacology,departamento de bioquímica e imunologia,instituto de ciências biológicas,universidade federal de minas gerais,belo horizonte,minas gerais, Brazil
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Authors
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