Age-associated oxidation of innate immune proteins in the lung mucosa alters the host response to Mycobacterium tuberculosis

Age-associated immune changes are a risk factor for the development of tuberculosis (TB); however the phenomenon of inflammaging, a state of heightened systemic inflammation observed in the elderly, particularly within the lung mucosa has not been addressed. Mycobacterium tuberculosis (M.tb) infection results in bacterial deposition in the lung alveoli where they are bathed in alveolar lining fluid (ALF). ALF contains soluble innate factors that mediate the M.tb-host cell encounter and subsequent immune response. Recent studies indicate that local inflammation and oxidation occur within the ALF. We hypothesize that ALF components lose their function as we age, and this deficiency favors the establishment of M.tb infection. Previously, we reported increased oxidation of proteins within ALF from human adult (ages 25–44) and elderly (ages >65) populations, in addition to elevated basal levels of inflammatory cytokines and complement components. Here, we extended our findings to explore the impact of adult or elderly ALF during M.tb infection. Although the levels of SP-A and C3 were elevated in elderly ALF, their binding to M.tb was reduced, suggesting a defect in innate immune function with age. To evaluate the impact of ALF age-associated changes in vivo, mice were infected with M.tb pre-exposed to adult or elderly ALF. Mice infected with elderly ALF-M.tb had significantly increased bacterial growth within the lung and spleen compared to adult ALF-M.tb infected mice, suggesting that loss of innate immune function within ALF could have long term consequences in controlling M.tb infection. We conclude that M.tb may benefit from the declining host defense function of the lung mucosa in the elderly, driving host susceptibility to TB.