title: Natural killer cells, dendritic cells, and the alarmin high-mobility group box 1 protein: a dangerous trio in HIV-1 infection?
abstract: OBJECTIVE
  Natural killer (NK) cells promote antiviral immunity by producing proinflammatory cytokines and by lysing infected cells. In addition, NK cells can modulate dendritic cell functions. NK-dendritic cell crosstalk results in activation of both cell types, with dendritic cells promoting NK-cell activity and NK cells inducing further maturation of dendritic cells. Here we review the recent evidence suggesting that NK-dendritic cell crosstalk is disrupted during HIV-1 infection and we discuss the consequences on HIV persistence in dendritic cells.
  
  
  RESULTS
  NK cell-mediated dendritic cell editing is compromised during HIV-1 infection, and NK cells from viremic individuals show a decreased ability to kill immature dendritic cells. The defect is associated with impaired NKp30 function. Moreover, the resistance of HIV-1-infected dendritic cells to NK-mediated lysis is associated with the upregulation of apoptosis inhibitors, thus protecting infected dendritic cells from TRAIL-dependent apoptosis. These inhibitors are upregulated by the high-mobility group box 1 protein (HMGB1), an alarmin produced at NK-dendritic cell synapse that is essential for NK-dependent dendritic cell maturation, but also promotes viral replication in infected dendritic cells.
  
  
  CONCLUSIONS
  HIV-1-induced impairment of NK-dendritic cell crosstalk may significantly alter both innate and adaptive immunity. It may also contribute to HIV persistence in dendritic cells through an HMGB1-dependent mechanism.
authors.affiliation: Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, Paris, France. marie-lise.gougeon@pasteur.fr
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Gougeon
authors.forename: Marlène
authors.initials: M
authors.lastname: Bras
mesh_terms: D056704:Adaptive Immunity; D003713:Dendritic Cells / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D024243:HMGB1 Protein / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*
chemical_list: D024243:HMGB1 Protein