TLR4 and cystic fibrosis: Interestingly, not only microorganisms can drive TLR signaling in the CF lung, but also microbleeds in the CF lung may result in the presence of heme, which can activate TLR signaling and inflammatory cytokine release in CFBE41o– CF cell line (Cosgrove et al., 2011), while increased neutrophil elastase is able to directly activate TLR4, ultimately leading to increased IL-8/CXCL-8 production (Devaney et al., 2003).