Abstract
Chronic obstructive pulmonary disease (COPD) is a complex chronic disease. Chronic inflammation is the hallmark of COPD, involving the interplay of a wide variety of cells in the lung microenvironment. Cigarette smoke (CS) induces chronic lung inflammation and is considered a key etiological factor in the development and pathogenesis of COPD. Structural and inflammatory cells in the lung respond to CS exposure by releasing proinflammatory mediators that recruit additional inflammatory immune cells, which collectively contribute to the establishment of a chronic inflammatory microenvironment. Chronic inflammation contributes to lung damage, compromises innate and adaptive immune responses, and facilitates the recurrent episodes of respiratory infection that punctuate and further contribute to the pathological manifestations of the stable disease. A number of studies support the conclusion that immune dysfunction leads to exacerbations and disease severity in COPD. Our group has clearly demonstrated that CS exacerbates lung inflammation and compromises immunity to respiratory pathogens in a mouse model of COPD. We have also investigated the phenotype of immune cells in patients with COPD compared with healthy control subjects and found extensive immune dysfunction due to the presence and functional activity of T regulatory cells, CD4(+)PD-1(+) exhausted effector T cells and myeloid-derived suppressor cells. Manipulation of these immunosuppressive networks in COPD could provide a rational strategy to restore functional immune responses, reduce exacerbations, and improve lung function. In this review, we discuss the role of immune dysfunction in COPD that may contribute to recurrent respiratory infections and disease severity.