title: Longitudinal Analysis of Natural Killer Cells in Dengue Virus-Infected Patients in Comparison to Chikungunya and Chikungunya/Dengue Virus-Infected Patients.
abstract: BACKGROUND
  Dengue virus (DENV) is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV). Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK) cells during DENV-2 infection is in its infancy.
  
  
  METHODS
  We performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients.
  
  
  RESULTS
  We observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ) by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV.
  
  
  CONCLUSIONS
  Although specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.|Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.
authors.forename: Caroline
authors.initials: C
authors.lastname: Petitdemange
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.|Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.|Metabiota, Inc., San Francisco, California, United States of America.
authors.forename: Nadia
authors.initials: N
authors.lastname: Wauquier
authors.affiliation: Internal Medicine and Systemic Diseases Department, Dijon University Hospital, Dijon, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Devilliers
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
authors.forename: Hans
authors.initials: H
authors.lastname: Yssel
authors.affiliation: Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.
authors.forename: Illich
authors.initials: I
authors.lastname: Mombo
authors.affiliation: Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Caron
authors.affiliation: Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.
authors.forename: Dieudonné
authors.initials: D
authors.lastname: Nkoghé
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.affiliation: Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.
authors.forename: Eric
authors.initials: E
authors.lastname: Leroy
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
mesh_terms: D000328:Adult; D065632:Chikungunya Fever / Q000150:complications* / Q000473:pathology*; D060085:Coinfection / Q000473:pathology; D003715:Dengue / Q000150:complications* / Q000473:pathology*; D005260:Female; D005681:Gabon; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male