title: Successive influenza virus infection and Streptococcus pneumoniae stimulation alter human dendritic cell function.
abstract: BACKGROUND
  Influenza virus is a major cause of respiratory disease worldwide and Streptococcus pneumoniae infection associated with influenza often leads to severe complications. Dendritic cells are key antigen presenting cells but its role in such co-infection is unclear.
  
  
  METHODS
  In this study, human monocyte derived-dentritic cells were either concurrently or successively challenged with the combination of live influenza virus and heat killed pneumococcus to mimic the viral pneumococcal infection. Dendritic cell viability, phenotypic maturation and cytokine production were then examined.
  
  
  RESULTS
  The challenge of influenza virus and pneumococcus altered dendritic cell functions dependent on the time interval between the successive challenge of influenza virus and pneumococcus, as well as the doses of pneumococcus. When dendritic cells were exposed to pneumococcus at 6 hr, but not 0 hr nor 24 hr after influenza virus infection, both virus and pneumococcus treated dendritic cells had greater cell apoptosis and expressed higher CD83 and CD86 than dendritic cells infected with influenza virus alone. Dendritic cells produced pro-inflammatory cytokines: TNF-α, IL-12 and IFN-γ synergistically to the successive viral and pneumococcal challenge. Whereas prior influenza virus infection suppressed the IL-10 response independent of the timing of the subsequent pneumococcal stimulation.
  
  
  CONCLUSIONS
  Our results demonstrated that successive challenge of dendritic cells with influenza virus and pneumococcus resulted in synergistic up-regulation of pro-inflammatory cytokines with simultaneous down-regulation of anti-inflammatory cytokine, which may explain the immuno-pathogenesis of this important co-infection.
authors.affiliation: Department of Paediatrics, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yuet
authors.initials: Y
authors.lastname: Wu
authors.forename: Huawei
authors.initials: H
authors.lastname: Mao
authors.forename: Man-To
authors.initials: MT
authors.lastname: Ling
authors.forename: Kin-Hung
authors.initials: KH
authors.lastname: Chow
authors.forename: Pak-Leung
authors.initials: PL
authors.lastname: Ho
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D010641:Phenotype; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D016207:Cytokines