Moraxella catarrhalis Activates Murine Macrophages through Multiple Toll Like Receptors and Has Reduced Clearance in Lungs from TLR4 Mutant Mice

摘要: Moraxella catarrhalis is a Gram negative bacterium and leading causative agent of otitis media (OM) in children. Several recent reports have provided strong evidence for an association between toll like receptors OM. It has been found that both Streptococcus pneumoniae nontypeable Haemophilus influenzae activate host protective immune responses through (TLRs), however, the precise mechanism by which initiates response currently unknown. In this report, using murine macrophages generated from series knock-out mice, we demonstrated M. lipooligosaccharide (LOS) either heat killed or live bacteria are recognized one more TLRs. LOS activates membrane bound CD14-TLR4 complex, while M.cat require recognition multiple such as TLR2, TLR4 TLR9 without requirement CD14. We also shown stimuli capable triggering innate MyD88- TRIF- dependent signaling pathways. further showed induced activation mitogen activated protein kinase (MAPK) essential order to achieve optimal secretion pro-inflammatory cytokine TNF-α. finally mutant C3H/HeJ mice produce significantly lower levels cytokines TNF-α IL-6 vivo, An increased bacterial loads at 12 24 hours (P<0.001) their lungs upon challenge with aerosol chamber compared wild-type (WT) control mice. These data suggest TLRs crucial effective M.cat. The results these studies contribute understanding molecular possible novel treatment strategies diseases caused specifically targeting