title: Invariant NKT cell response to dengue virus infection in human.
abstract: BACKGROUND
  Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their role in human dengue virus infection is not known. We hypothesized that iNKT cells play a role in human dengue infection.
  
  
  METHODS
  Blood samples from a well-characterized cohort of children with DF, DHF, in comparison to non-dengue febrile illness (OFI) and healthy controls at various time points were studied. iNKT cells activation were analyzed by the expression of CD69 by flow cytometry. Their cytokine production was then analyzed after α-GalCer stimulation. Further, the CD1d expression on monocytes, and CD69 expression on conventional T cells were measured.
  
  
  RESULTS
  iNKT cells were activated during acute dengue infection. The level of iNKT cell activation associates with the disease severity. Furthermore, these iNKT cells had altered functional response to subsequent ex vivo stimulation with α-GalCer. Moreover, during acute dengue infection, monocytic CD1d expression was also upregulated and conventional T cells also became activated.
  
  
  CONCLUSIONS
  iNKT cells might play an early and critical role in the pathogenesis of severe dengue viral infection in human. Targeting iNKT cells and CD1d serve as a potential therapeutic strategy for severe dengue infection in the future.
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Systems Biology of Diseases Research Unit, Faculty of Science, Mahidol University, Bangkok, Thailand; Center of Emerging and Neglected Infectious Diseases, Mahidol University, Bangkok, Thailand.
authors.forename: Ponpan
authors.initials: P
authors.lastname: Matangkasombut
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Wilawan
authors.initials: W
authors.lastname: Chan-In
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Anunya
authors.initials: A
authors.lastname: Opasawaschai
authors.affiliation: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Pisut
authors.initials: P
authors.lastname: Pongchaikul
authors.affiliation: Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
authors.forename: Nattaya
authors.initials: N
authors.lastname: Tangthawornchaikul
authors.affiliation: Department of Pediatrics, Khon Kaen Hospital, Khon Kaen, Thailand.
authors.forename: Sirijitt
authors.initials: S
authors.lastname: Vasanawathana
authors.affiliation: Department of Pediatrics, Songkhla hospital, Songkhla, Thailand.
authors.forename: Wannee
authors.initials: W
authors.lastname: Limpitikul
authors.affiliation: Center of Emerging and Neglected Infectious Diseases, Mahidol University, Bangkok, Thailand; Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand; Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.affiliation: Center of Emerging and Neglected Infectious Diseases, Mahidol University, Bangkok, Thailand; Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand.
authors.forename: Thaneeya
authors.initials: T
authors.lastname: Duangchinda
authors.affiliation: Division of Immunology and Inflammation, Department of Medicine, Hammersmith campus, Imperial College London, London, United Kingdom.
authors.forename: Gavin
authors.initials: G
authors.lastname: Screaton
authors.affiliation: Center of Emerging and Neglected Infectious Diseases, Mahidol University, Bangkok, Thailand; Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; Division of Immunology and Inflammation, Department of Medicine, Hammersmith campus, Imperial College London, London, United Kingdom.
authors.forename: Juthathip
authors.initials: J
authors.lastname: Mongkolsapaya
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D055610:Antigens, CD1d / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D007223:Infant; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000821:virology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000821:virology; D019595:Severe Dengue / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D005699:Galactosylceramides; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C526877:CD1D protein, human; C493154:alpha-galactosylceramide