Effect of the elderly human lung mucosa on Mycobacterium tuberculosis infection of the alveolar epithelium

Abstract

Abstract As we age, there is an increased risk for developing tuberculosis (TB), a disease caused by the infectious agent Mycobacterium tuberculosis (M.tb). M.tb infection results in a bacterial deposition in the lung alveolus, where M.tb is bathed in alveolar lining fluid (ALF). We have published that age-associated changes in human ALF soluble components, such as increased levels of oxidized and dysfunctional innate proteins, accelerate M.tb growth within human alveolar macrophages. We are interested in studying the impact of human ALF on M.tb infection of non-professional phagocytes, such as alveolar epithelial cells (ATs). We hypothesized that M.tb exposure to elderly human ALF (E-ALF) drives increased M.tb replication and growth within ATs due to impairment of E-ALF innate soluble components. We observed that E-ALF exposed M.tb had significantly increased intracellular growth in ATs. Despite changes in intracellular bacterial growth, infected ATs with E-ALF-exposed M.tb did not show altered production of inflammatory mediators or cell activation. Interestingly, M.tb exposure to E-ALF did not alter intracellular trafficking, but it drove bacterial translocation to both endosomal and cytosolic compartments in ATs. Overall, rapid bacterial replication and increased growth within ATs was observed in M.tb exposed to E-ALF, and together with inadequate AT activation, could lead M.tb to potentially exploit the AT cytosol as a favorable intracellular niche for replication. These results emphasize the effects of elderly lung mucosa on M.tb infection of non-professional phagocytes (ATs), which may conceivably explain why the elderly population is more vulnerable to developing active TB disease.