Cystic Fibrosis Lung Immunity: The Role of the Macrophage

Abstract

Cystic fibrosis (CF) pathophysiology is hallmarked by excessive inflammation and the inability to efficiently resolve lung infections, contributing to major morbidity and eventually the mortality of patients with this disease. Macrophages (MΦs) are major players in lung homeostasis through their diverse contributions to both the innate and adaptive immune networks. The setting of MΦ function and activity in CF is multifaceted, encompassing the response to the unique environmental cues in the CF lung as well as the intrinsic changes resulting from CFTR dysfunction. The complexity is further enhanced with the identification of modifier genes, which modulate the CFTR contribution to disease, resulting in epigenetic and transcriptional shifts in MΦ phenotype. This review focuses on the contribution of MΦ to lung homeostasis, providing an overview of the diverse literature and various perspectives on the role of these immune guardians in CF.

Fig. 1

A summary of abnormalities described in CF MΦs that lead to proinflammatory behavior (a) and suboptimal phagocytosis (b). Potential molecular mechanisms associated with these suboptimal performances are listed.

Fig. 2

The figure emphasizes the ‘team’ function of MΦ contribution to immune function and the potential contributions to CF lung pathophysiology. MΦs, when dysfunctional, may not only alter their important role in healthy lung homeostasis, but also impact the surrounding immune community. T-cell communication networks through MΦ MHC class II (defined by genomic correlations), with the potential of contributing to inefficient B-cell, T-cell and NK-cell activity, suggesting downstream pathophysiology associated with MΦ dysfunction.