Innate immune responses in the ageing lung

Abstract

The world is undergoing an unprecedented shift in demographics, with the number of individuals over the age of 60 years projected to reach 2 billion or more by 2050, representing 22% of the global population. Elderly people are at a higher risk for chronic disease and more susceptible to infection, due in part to age-related dysfunction of the immune system resulting from low-grade chronic inflammation known as 'inflamm-ageing'. The innate immune system of older individuals exhibits a diminished ability to respond to microbial threats and clear infections, resulting in a greater occurrence of many infectious diseases in elderly people. In particular, the incidence of and mortality from lung infections increase sharply with age, with such infections often leading to worse outcomes, prolonged hospital stays and life-threatening complications, such as sepsis or acute respiratory distress syndrome. In this review, we highlight research on bacterial pneumonias and pulmonary viral infections and discuss age-related changes in innate immunity that contribute to the higher rate of these infections in older populations. By understanding more clearly the innate immune defects in elderly individuals, we can design age-specific therapies to address lung infections in such a vulnerable population.

Keywords: aging; infection; inflammation; lung; macrophages; neutrophils; pneumonia.

Figure 1

Innate immune functions of alveolar macrophages. As the resident innate immune cell of the pulmonary airspace, alveolar macrophages stand at the forefront of host defence against microbial invaders in the lung. Along with their role in effecting and propagating the inflammatory response by phagocytosing microbes and secreting proinflammatory mediators, alveolar macrophages also facilitate resolution by clearing away dead cells (efferocytosis) and producing anti‐inflammatory mediators.

Figure 2

Dysregulated Toll‐like receptor signalling associated with advanced age. This figure depicts signalling pathways downstream of Toll‐like receptor signalling, some of which have been shown to be disrupted or altered with age. Dashed red boxes indicate specific pathway components known to be affected by ageing, as discussed in this review 29, 30, 31, 32, 33, 34.