title: A detrimental role for invariant natural killer T cells in the pathogenesis of experimental dengue virus infection.
abstract: Dengue virus (DENV), a member of the mosquito-borne flaviviruses, is a serious public health problem in many tropical countries. We assessed the in vivo physiologic contribution of invariant natural killer T (iNKT) cells, a population of nonconventional lipid-reactive αβ T lymphocytes, to the host response during experimental DENV infection. We used a mouse-adapted DENV serotype 2 strain that causes a disease that resembles severe dengue in humans. On DENV challenge, splenic and hepatic iNKT cells became activated insofar as CD69 and Fas ligand up-regulation and interferon-γ production. C57BL/6 mice deficient in iNKT cells (Jα18(-/-)) were more resistant to lethal infection than were wild-type animals, and the phenotype was reversed by adoptive transfer of iNKT cells to Jα18(-/-) animals. The absence of iNKT cells in Jα18(-/-) mice was associated with decreased systemic and local inflammatory responses, less liver injury, diminished vascular leak syndrome, and reduced activation of natural killer cells and neutrophils. iNKT cell functions were not necessary for control of primary DENV infection, after either natural endogenous activation or exogenous activation with the canonical iNKT cell agonist α-galactosylceramide. Together, these data reveal a novel and critical role for iNKT cells in the pathogenesis of severe experimental dengue disease.
authors.affiliation: Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Université Lille Nord de France, Lille, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Renneson
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Guabiraba
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maillet
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Marques
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.forename: Josette
authors.initials: J
authors.lastname: Fontaine
authors.forename: Christophe
authors.initials: C
authors.lastname: Paget
authors.forename: Valérie
authors.initials: V
authors.lastname: Quesniaux
authors.forename: Christelle
authors.initials: C
authors.lastname: Faveeuw
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: François
authors.initials: F
authors.lastname: Trottein
mesh_terms: D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000096:biosynthesis; D003715:Dengue / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D018375:Neutrophil Activation / Q000276:immunology; D016019:Survival Analysis; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000502:physiology
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; D018836:Inflammation Mediators; C493154:alpha-galactosylceramide