Innate immunity and chronic obstructive pulmonary disease: a mini-review

Abstract

Chronic obstructive pulmonary disease (COPD), a major smoking-associated lung disorder characterized by progressive irreversible airflow limitation, affects >200 million people worldwide. Individuals with COPD have increased susceptibility to respiratory infections, resulting in exacerbations of the disease. A growing body of evidence indicates that multiple host defense mechanisms, such as those provided by the airway epithelial barrier and innate immune cells, including alveolar macrophages, neutrophils, dendritic cells and natural killer cells, are broadly suppressed in COPD in a smoking-dependent manner. Inactivation of the innate immune system observed in COPD smokers is remarkably similar to the immunosenescence phenotype associated with aging. As a consequence of defective innate immune defense, the lungs of COPD smokers are frequently colonized with pathogens and commonly develop bacterial and viral infections, which cause secondary inflammation, a major driver of the disease progression. In this review, we summarize the evidence from human studies related to disordering of the innate immune system in COPD, discuss possible relationships between those changes and aging, and provide insights into potential therapeutic strategies aimed at the prevention of COPD progression via normalization of the disordered innate immune mechanisms.

Figure 1. The role of disordered innate immunity in COPD pathogenesis

Various environmental and endogenous factors determine the status of the innate immune system in the lung, which includes the airway epithelial barrier composed of different populations of airway epithelial cells (ciliated, mucus-producing, secretory Clara, basal cells) connected to each other via apical junctions, and host defense cells of the hematopoietic origin such as alveolar macrophages, dendritic cells, neutrophils, and NK cells. Chronic exposure to cigarette smoke and other harmful factors, as well as endogenous processes in the lung such as aging and pathological changes associated with prior diseases can suppress the host defense potential of the innate immune mechanisms in the lung, leading to increased susceptibility to respiratory infections which cause secondary inflammation and, thereby, contribute to lung tissue destruction and progressive decline in lung function in COPD patients. In addition, COPD-associated inflammation and tissue damage further suppress innate immune mechanisms in the lung.