Aging is a major risk factor for both the development of primary tuberculosis (TB) disease and for theconversion of latent Mycobacterium tuberculosis (M.tb) infection to active TB disease. As a consequence,persons over the age of 65 have the highest TB case rate and are the most susceptible to TB associateddeath. The immunological factors that contribute to the increased susceptibility of the elderly to TB remainlargely unknown. The overarching hypothesis of this program project is that specific changes in inflammatorypathways (termed inflammaging) mediate unique and sub-optimal re-programming in pulmonary and systemicimmunity during aging, and worsen the outcome of M.tb infection in the elderly. Project 1 will analyze howpulmonary surfactant and complement contribute to the loss of alveolar complexity within the aging lung andmodify the initial cellular interaction with M.tb. Project 2 will address age-associated changes in the function ofalveolar macrophages and how they affect M.tb infection. Project 3 will determine the impact of aging andinflammaging on control of primary and latent M.tb infection in old mice. Project 4 will investigate M.tb specificmonocyte and T cell function in elderly subjects with latent or active TB. Altogether, these studies will providemechanistic information to understand how inflammaging and immune senescence impact M.tb infection in theelderly. The program brings together an established group of collaborative scientists with expertise in clinicalTB, TB pathogenesis and the immune response to infection, the latter both in human and animal models.
Increasing age is a major risk factor for primary TB infection and the conversion of latent TB infection to activeTB disease. We propose to elucidate how a process called inflammaging alters M.tb control in the elderly. Ourfindings will contribute to improving the diagnosis; treatment and prevention of TB in the elderly.
