Immune Dysfunction in Cystic Fibrosis

Absence of the cystic fibrosis transmembrane regulator (CFTR) function leads to chronic lung disease characterized by inflammation and persistent infections. The mechanisms for the increased susceptibility of the respiratory tract for infections in CF are most likely complex and only partially understood. Most attention has been focused on the effect of the defective expression of CFTR in epithelial cells and submucosal gland cells and the increased susceptibility of the respiratory tract to infections was was mostly thought to be related to the abnormal chloride channel function (Welsh MJ, 2011, Ratjen F 2003). However, numerous studies over the past years have shown that the absence of CFTR affects the immune system and that dysfunctional immune responses contribute to pathological processes in the CF lung. In addition, it has become increasingly evident that the chloride channel dysfunction alone cannot completely explain the pathology of CF lung disease and that other pathways known to be regulated by CFTR play a role in the immune dysregulation in the CF lung (Mehta A 2008). This chapter reviews both soluble factors in the CF milieu that modify immune cell function and specific alterations in the cellular components of the innate and adaptive immune system that contribute to the impaired immune defense in CF lung disease.