In the present study, we used 3 cellular models (Figure 1 and Table 1) to capture the impact of the intrinsic deficiency (CFTR mutation) on circulating immune cells as well as the impact of the unhealthy immune microenvironment and compromised inflammatory milieu on circulating immune cells—particularly monocytes and macrophages—in CF probands and carrier parents. Here, CFTR is linked to cystic fibrosis.