title: Toll-like receptor 6 V327M polymorphism is associated with an increased risk of Klebsiella pneumoniae infection.
abstract: BACKGROUND
  Klebsiella pneumoniae is a common cause of nosocomial pneumonia, especially in children. Toll-like receptors plays an important role in defense against this pathogen. The impact of human TLR6 polymorphisms on susceptibility to K. pneumoniae infection is poorly understood. The aim of the present work was to determine whether single nucleotide polymorphisms in TLR6 are associated with altered immune responses to K. pneumoniae.
  
  
  METHODS
  The TLR6 coding region was sequenced in 126 K. pneumoniae culture-positive patients and 142 hospitalized K. pneumoniae culture-negative controls.
  
  
  RESULTS
  The frequency of V327M polymorphism was found to be significantly higher in patients than that in controls (16.7% vs. 7.7%). In vitro studies showed that V327M polymorphism did not impair TLR6 expression in transfected HEK 293T cells. Further studies demonstrated that V327M polymorphism was associated with increased IL-8 mRNA expression in transfected HEK 293T cells when stimulated with K. pneumoniae and the specific ligand for TLR2/TLR6 heterodimers known as Pam2CSK4. The present data showed V327M polymorphism to be associated with increased apoptosis of HEK 293T cells when challenged with K. pneumoniae.
  
  
  CONCLUSIONS
  Taken together, these data indicated that TLR6 V327M may be involved in mediating deleterious inflammatory responses and modulating host susceptibility to K. pneumoniae. These results provide new insight into the pathophysiologic role of TLR6 V327M in the innate immune response to bacterial infection in human.
authors.affiliation: From the Department of Laboratory Medicine, Shanghai Children's Medical Center,Shanghai Jiaotong University School of Medicine,Shanghai, P.R. China.
authors.forename: Haiou
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Geng
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Zheng
authors.forename: Qihua
authors.initials: Q
authors.lastname: Fu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D018920:Coculture Techniques; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D007710:Klebsiella Infections / Q000235:genetics* / Q000382:microbiology; D007711:Klebsiella pneumoniae; D055666:Lipopeptides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D016209:Interleukin-8; D055666:Lipopeptides; D016328:NF-kappa B; C560312:Pam2CSK4 lipopeptide; D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6