title: Pretreatment with TLR2 and TLR4 ligand modulates innate immunity in corneal fibroblasts challenged with Aspergillus fumigatus.
abstract: OBJECTIVE
  To study the innate immunity in telomerase-immortalized human stroma fibroblasts (THSFs) challenged with Aspergillus fumigatus hyphae after copretreatment with TLR2 and TLR4 ligand.
  
  
  METHODS
  THSFs were pretreated with different concentrations of zymosan and/or lipopolysaccharide (LPS) at different time periods, and challenged with high-dose Aspergillus fumigatus hyphae. The gene expression and protein secretion of inflammatory cytokines (TNF-α, IL-6, and IL-8) were detected by RT-PCR and ELISA. The effects of stimulation or pretreatment of TLR ligands on proliferation of THSFs were measured by MTT analysis.
  
  
  RESULTS
  In the certain concentration range, pretreatment of THSFs with zymosan suppressed gene expression of inflammatory cytokines (TNF-α and IL-6). Copretreatment with zymosan and LPS suppressed gene expression and protein secretion more strongly compared with pretreatment with zymosan or LPS alone. Zymosan and/or LPS pretreatment suppressed lethal effect of A. fumigatus to THSFs in a certain period.
  
  
  CONCLUSIONS
  Pretreatment of THSFs with TLR2-specific ligand zymosan results in a state of A. fumigatus hyphae tolerance. Copretreatment with TLR2 and -4 ligands (zymosan and LPS) leads to a stronger state of A. fumigatus hyphae tolerance, and suppresses the lethal effect of A. fumigatus.
authors: Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
authors: Yingchao
authors: Y
authors: Li
authors: Hongling
authors: H
authors: Yang
authors: Xinyi
authors: X
authors: Wu
mesh_terms: D001232:Aspergillus fumigatus / Q000472:pathogenicity*; D049109:Cell Proliferation; D060527:Corneal Keratocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D003319:Corneal Stroma / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D008024:Ligands; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015054:Zymosan
keywords: Aspergillus fumigatus; cytokines; human stroma fibroblasts; lipopolysaccaride; zymosan