RT Journal Article SR Electronic T1 Toll-like receptor (TLR)-signaling mediates enhanced inflammatory effects in coinfections of viral and bacterial respiratory pathogens in human lung tissue – A new approach to the pathogenesis of COPD exacerbations? JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP p3504 VO 38 IS Suppl 55 A1 Kristina Rohmann A1 Enguo Chen A1 Jan Rupp A1 Torsten Goldmann A1 Daniel Droemann A1 Klaus Dalhoff YR 2011 UL http://erj.ersjournals.com/content/38/Suppl_55/p3504.abstract AB Acute exacerbations of COPD are mainly mediated by respiratory viruses or bacteria like nontypeable Haemophilus influenzae (NTHi) and Chlamydia pneumoniae (Cpn). To elucidate inflammatory responses to coinfections, we investigated the interaction of viral/atypical pathogens and NTHi in respiratory cells and human lung tissue with the TLR3-agonist Poly(I:C) as a model of viral infection and Cpn as an atypical, TLR2-inducing agent.Alveolar Epithelial Cells (AEC) and human lung tissue (HLT) were pre-incubated with Poly(I:C) or Cpn (strain CWL-029) and costimulated with NTHi 106cfu/ml (strain Rd KW20). After 24h cells and supernatants were harvested for ELISA and Western Blot analysis and tissue was used for in situ-Hybridisation (ISH).NTHi led to significant induction of Interleukin-8 (IL-8) production (HLT: Med 134848±22483pg/ml vs. NTHi 341926±34390pg/ml, n=12, p<0.01). NTHi and Poly(I:C) increased IL-8-production and had significant costimulatory effects as well as Cpn/NTHi-coinfection (AEC: NTHi+Poly(I:C) 18.48±1.93ng/ml vs. NTHi 8.70±2.22ng/ml, p< 0.05, n=4; HLT: Cpn 199395±32882pg/ml vs. Cpn+NTHi 364777±53085pg/ml, p<0.05, n=6). TLR3- and TLR2-stimulation were mediated via MAP-kinases. ISH showed increased IL-8-and TLR2-expression in HLT after Cpn/NTHi-coinfection. Blocking TLR2 with a specific antibody led to partial reduction of IL-8.These data indicate that TLR2- and TLR3-stimulation are necessary for inflammatory responses in NTHi-infection and that TLR-signaling might be important for enhanced inflammation in viral/NTHi and atypical/NTHi coinfections.