title: Exogenous C3 protein enhances the adaptive immune response to polymicrobial sepsis through down-regulation of regulatory T cells.
abstract: BACKGROUND
  The role of complement system in bridging innate and adaptive immunity has been confirmed in various invasive pathogens. It is still obscure how complement proteins promote T cell-mediated immune response during sepsis. The aim of this study is to investigate the role of exogenous C3 protein in the T-cell responses to sepsis.
  
  
  METHODS
  Sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type C57BL/6 mice, sham-operated mice for control. Human purified C3 protein (HuC3, 1 mg) was intraperitoneally injected at 6 h post-surgery, with 200 μl phosphate-buffered saline as control. The levels of C3 and cytokines, the expression of FOXP3 and NF-κB, and the percentages of CD4(+) T-cell subsets were compared among the groups at given time points.
  
  
  RESULTS
  The polymicrobial sepsis produced considerable release of TNF-α and IL-10, and caused complement C3 exhaustion. Exogenous C3 administration markedly improved the 48 h survival rate, as compared with nontreatment (40% vs. 5%, P<0.01). The expression of FOXP3 protein was increased during sepsis, but can be suppressed by HuC3 administration. A single injection of HuC3 postponed the decline of differentiated Th1 cells, and depressed the activation of Th2/Th17 cells. Besides, the Th1-Th2 shift in late stage of sepsis can be controlled under C3 supplementation. The suppression of NF-κB pathway might be related to the appearance of immunocompromise.
  
  
  CONCLUSIONS
  The study confirmed the important role of exogenous C3 in up-regulation of adaptive immune response to sepsis. The complement pathway would be a pivotal target for severe sepsis management.
authors.affiliation: Department of Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jianan
authors.initials: J
authors.lastname: Ren
authors.forename: Shougen
authors.initials: S
authors.lastname: Cao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D003176:Complement C3 / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology; D018805:Sepsis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C038245:C3 protein, human; D003176:Complement C3; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10