The Role of Toll-like Receptors in Age-Associated Lung Diseases

The aging lung is faced with unique challenges. The lungs are the only internal organ with a direct interface with both the internal and the external environments and as a consequence are constantly sampling diverse, potentially injurious, elements. Therefore, the lungs have evolved a sophisticated, multilayered detection system to distinguish low-level, nonharmful signals from those that are toxic. A family of innate immune receptors, Toll-like receptors (TLRs), appears to serve such a function. Initially described as pattern-recognition receptors that recognize and protect against microbes, TLRs can also respond to diverse, nonmicrobial signals. The role of Toll-like receptors in noninfectious, age-related chronic lung disease is poorly understood. This review presents our current understanding of the biology of age-related lung diseases with a focus on the role of Toll-like receptors in idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and late-onset asthma.