Malfunctioning of the CFTR, along with accumulation of the misfolded channel, in the case of ΔF508 homozygous patients, induces a perpetual chronic low-grade inflammation in CF macrophages, predisposing these cells to a hyper-inflammatory and metabolic response, driven by XBP1s, which is exacerbated by the activation of TLR4 (Figure 7) and may be unresolved due to the lack of M2 macrophage polarization. Here, TLR4 is linked to cystic fibrosis.