Respiratory infection and the impact of pulmonary immunity on lung health and disease

Abstract

Acute lower respiratory tract infection is responsible for an inordinate disease burden. Pulmonary immunity determines the outcomes of these infections. The innate and adaptive immune responses to microbes in the lung are critical to maintaining a healthy respiratory system and preventing pulmonary disease. In addition to balancing antimicrobial defense against the risk of lung injury during the immediate infection, the shaping of pulmonary immunity by respiratory infection contributes to the pathophysiology of many and even perhaps most chronic pulmonary diseases. This Pulmonary Perspective aims to communicate two interconnected points. First, tremendous morbidity and mortality result from inadequate, misguided, or excessive pulmonary immunity. Second, our understanding of pulmonary immunity is at an exciting stage of rapid developments and discoveries, but many questions remain. Further advances in pulmonary immunity and elucidation of the cellular and molecular responses to microbes in the lung are needed to develop novel approaches to predicting, preventing, and curing respiratory disease.

Figure 1.

Disease caused by acute lower respiratory infection. (A) Total worldwide burden of select diseases, as assessed by disability-adjusted life years (DALYs) lost reported by the World Health Organization (WHO) (2). Diseases directly related to pulmonary immunity are highlighted with colored bars. Figures represent Standard DALYs for 2004. (B) Trends in U.S. mortality due to pneumonia and influenza through the 20th century. (Data provided by Dr. Gregory L. Armstrong, U.S. Centers for Disease Control and Prevention, Atlanta, GA, as previously reported [3]). Four distinct trends are differentiated. (C) The relative numbers of deaths in the United States attributed to any infection or lung disease, based on data from the National Vital Statistics System (7). International Classification of Diseases codes included were as follows: Lung cancer C33–C34, COPD J40–J44; Acute lung infection J10–J18; Septicemia A40–A41; HIV/AIDS B20–B24; Intestinal infections A00–A09; Asthma J45–J46; and Tuberculosis A16–A19. The category “Other” includes all deaths attributed to “Diseases of the respiratory system (J00–J98)” or “Certain infectious or parasitic diseases (A00–B99)” other than the above. (D) The top 10 most common reasons U.S. children are hospitalized, based on data from the Healthcare Cost and Utilization Project (9). Colored bars represent hospitalizations resulting from alterations in pulmonary immunity, with red reflecting acute lower respiratory infection directly. Acute Lung Infection = WHO categories Lower Respiratory Infections plus Pertussis; Alzheimer/dementias = Alzheimer and other dementias, and other diseases as identified by the WHO; COPD = chronic obstructive pulmonary disease; Depression = unipolar depressive disorders; Neoplasms = malignant neoplasms; subcu = subcutaneous.

Figure 2.

Respiratory infections and dynamic pulmonary immunity. The schematic depicts a stylized lung unit with airway and alveolar air spaces surrounded by epithelium, changing over time due to infection (red I with open arrow). The following cells are highlighted: alveolar macrophages (A), neutrophils (N), inflammatory monocyte/macrophages (m), stem cells (S), and lymphocytes (L). Different stages of the responses to infection are identified, as well as consequences of dysregulated processes in these steps.