In aggregate, the presented results support that TLR5 promotes TLR4 signaling in several models of TLR4 activation through pathogen- or danger-associated molecular patterns (PAMPs or DAMPs, that is LPS or hyaluronan respectively) and promotes TLR4-mediated inflammation and airway hyperresponsiveness in vivo. Here, TLR4 is linked to airway hyperresponsiveness.