Innate receptors and cellular defense against pulmonary infections

Abstract

In the United States, lung infections consistently rank in the top 10 leading causes of death, accounting for >50,000 deaths annually. Moreover, >140,000 deaths occur annually as a result of chronic lung diseases, some of which may be complicated by an infectious process. The lung is constantly exposed to the environment and is susceptible to infectious complications caused by bacterial, viral, fungal, and parasitic pathogens. Indeed, we are continually faced with the threat of morbidity and mortality associated with annual influenza virus infections, new respiratory viruses (e.g., SARS-CoV), and lung infections caused by antibiotic-resistant "ESKAPE pathogens" (three of which target the lung). This review highlights innate immune receptors and cell types that function to protect against infectious challenges to the respiratory system yet also may be associated with exacerbations in chronic lung diseases.

Figure 1

(A) The lung at baseline is constantly exposed to fungal spores, bacteria and viral particles through alveolar macrophages phagocytosis, IFN production by epithelial cells and the mucocilliary escalator. (B) If these defenses become overwhelmed during an active infection, a robust inflammatory process involving alveolar macrophages, DCs, γδ T cells, ILCs, neutophils and epithelial cells commences and involves a variety of antimicrobial mediators. (C) However, during persistent exposure, the inflammatory response remains, contributing to the exacerbation of chronic lung diseases like COPD and asthma through an abundance of neutrophils, Th2/Th17, ILC2 and ILC3 cells.