Abstract
Tuberculosis (TB) is the leading killer due to a single infectious disease worldwide. With the aging of the global population, the case rate and deaths due to TB are highest in the elderly population. While general immunosenescence associated with old age is thought to contribute to the susceptibility of the elderly to develop active TB disease, very few studies of immune function in elderly individuals with Mycobacterium tuberculosis (M.tb) infection or disease have been performed. In particular, impaired adaptive T cell immunity to M.tb is one proposed mechanism for the elderly's increased susceptibility primarily on the basis of the decreased delayed type hypersensitivity response to tuberculin-purified protein derivative in the skin of elderly individuals. To investigate immunological reasons why the elderly are susceptible to develop active TB disease, we performed a cross-sectional observational study over a five year period (2012-2016) enrolling participants from 2 age groups (adults: 25-44 years; elderly: 65 and older) and 3 M.tb infection statuses (active TB, latent TB infection, and healthy controls without history of M.tb infection). We hypothesized that impaired peripheral T cell immunity plays a role in the biological susceptibility of the elderly to TB. Contrary to our hypothesis, we observed no evidence of impaired M.tb specific T cell frequency or altered production of cytokines implicated in M.tb control (IFN-γ, IL-10) in peripheral blood in the elderly. Instead, we observed alterations in monocyte proportion and phenotype with age and M.tb infection that suggest their potential role in the susceptibility of the elderly to develop active TB. Our results suggest a potential link between the known widespread low-grade systemic inflammation of old age, termed "inflammaging," with the elderly's specific susceptibility to developing active TB. Moreover, our results highlight the need for further research into the biological reasons why the elderly are more susceptible to disease and death from TB, so that public health systems can be better equipped to face the present and future problem of TB in an aging global population.
Highlights
Subjects excluded from analysis mostly included those whose samples were used for assay standardization or who had a previous history of treatment for active TB or latent TB infection (LTBI). 6 study groups were defined for our primary analysis, with 2 age groups and 3 M.tb infection statuses
All but 3 subjects with active TB were culture confirmed to have M.tb complex, with the other three diagnoses being clinical TB uveitis disease which improved on TB treatment and two subjects with pleural TB diagnosed based on abnormal chest x-ray and chest-computed tomography (CT) and improvement following TB treatment
From available epidemiologic data (CDC, 2017; Negin et al, 2015; WHO, 2017), it is clear that changes incident to age contribute to the likelihood of the elderly to die from an episode of active TB
Summary
T cell responses to specific latency-associated antigens of M.tb have been investigated in the elderly, though without specific comparison to younger cohorts (Commandeur et al, 2011) These studies, taken together, do not provide definitive proof that age-related changes in T cell function contribute to risk of active TB in the elderly. To provide additional investigation of immunological reasons why the elderly are susceptible to develop active TB, we performed a cross-sectional observational study over a five year period (2012–2016) enrolling participants from 2 age groups (adults: 25–44 years; elderly: 65 and older) and 3 M.tb infection statuses (active TB, LTBI, and healthy controls without history of M.tb infection). Our results suggest a potential link between the known widespread low-grade systemic inflammation of old age, termed “inflammaging,” with the elderly’s specific susceptibility to developing active TB (Franceschi and Campisi, 2014; Piergallini and Turner, 2017)
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