Growing old is associated with an increase in the basal inflammatory state of an individual and susceptibility to many diseases, including infectious diseases. Evidence is growing to support the concept that inflammation and disease susceptibility in the elderly is linked. Our studies focus on the infectious disease tuberculosis (TB), which is caused by Mycobacterium tuberculosis (M.tb), a pathogen that infects approximately one fourth of the world's population. Aging is a major risk factor for developing TB, and inflammation has been strongly implicated. In this review we will discuss the relationship between inflammation in the lung and susceptibility to develop and succumb to TB in old age. Further understanding of the relationship between inflammation, age, and M.tb will lead to informed decisions about TB prevention and treatment strategies that are uniquely designed for the elderly.

Mycobacterium bovis bacillus Calmette–Guérin (BCG) immunization still remains the best vaccination strategy available to control the development of active tuberculosis. Protection afforded by BCG vaccination gradually wanes over time and although booster strategies have promise, they remain under development. An alternative approach is to improve BCG efficacy through host-directed therapy. Building upon prior knowledge that blockade of IL-10R1 during early Mycobacterium tuberculosis infection improves and extends control of M. tuberculosis infection in mice, we employed a combined anti–IL-10R1/BCG vaccine strategy. An s.c. single vaccination of BCG/anti–IL10-R1 increased the numbers of CD4+ and CD8+ central memory T cells and reduced Th1 and Th17 cytokine levels in the lung for up to 7 wk postvaccination. Subsequent M. tuberculosis challenge in mice showed both an early (4 wk) and sustained long-term (47 wk) control of infection, which was associated with increased survival. In contrast, protection of BCG/saline-vaccinated mice waned 8 wk after M. tuberculosis infection. Our findings demonstrate that a single and simultaneous vaccination with BCG/anti–IL10-R1 sustains long-term protection, identifying a promising approach to enhance and extend the current BCG-mediated protection against TB.

Individuals over the age of 65 are highly susceptible to infectious diseases, which account for one-third of deaths in this age group. Vaccines are a primary tool to combat infection, yet they are less effective in the elderly population. While many groups have aimed to address this problem by studying vaccine-induced peripheral blood responses in the elderly, work from our lab and others demonstrate that immune responses to vaccination and infectious challenge may differ between tissue sites and the periphery. In this pilot study, we established an in vivo delayed-type hypersensitivity model of Mycobacterium bovis BCG vaccination and tuberculin skin test in two adult and two aged baboons. Vaccination generates BCG-specific immune cells that are recruited to the skin upon tuberculin challenge. We tested short term recall responses (8 weeks post-vaccination) and long term recall responses (25 weeks post-vaccination) by performing skin punch biopsies around the site of tuberculin injection. In short term recall responses, we found increased oxidation and decreased production of immune proteins in aged baboon skin at the site of TST challenge, in comparison to adult skin. Differences between adult and aged animals normalized in the long term response to tuberculin. In vitro, aged peripheral blood mononuclear cells had increased migration and functional responses to antigen-specific stimulation, suggesting that age-related changes in the tissue in vivo impairs aged immune recall responses to antigenic challenge. These findings highlight the impact of age-associated changes in the local tissue environment in memory recall responses, which may be more broadly applied to the study of other tissues. Moreover, these findings should be considered in future studies aimed at understanding and improving aging immune responses to vaccination and tissue challenge.

Mycobacterium tuberculosis , the causative agent of tuberculosis disease, is estimated to infect one-fourth of the world’s population and is one of the leading causes of death due to an infectious disease worldwide. The high-level variability in tuberculosis disease responses in the human populace may be linked to immune processes related to inflammation.