Abstract
Reactivation of latent tuberculosis (LTBI) is more common among the aging population and may contribute to increased transmission in long-term health care facilities. Difficulties in detecting LTBI due to potential blunting of the tuberculin skin test (TST), and the lowered ability of the elderly to tolerate the course of antibiotics, underscore the need for an effective vaccine. Immuno-senescence reduces the capacity of vaccines to induce sufficient levels of protective immunity against many pathogens, further increasing the susceptibility of the elderly to infectious diseases. We sought to evaluate the response of B cells to Mycobacterium tuberculosis (Mtb) in residents of long-term care facilities to determine the feasibility of using a vaccine to control infection and transmission from reactivated LTBI. Our results demonstrate that although B cell responses were higher in subjects with LTBI, Mtb antigens could stimulate B cell activation and differentiation in vitro in TST negative subjects. B cells from elderly subjects expressed high basal levels of Toll-like receptor (TLR)2 and TLR4 and responded strongly to Mtb ligands with some activation pathways dependent on TLR2. B cells derived from blood, tonsil and spleen from younger subjects responded similarly and to the same magnitude. These results suggest that B cell responses are robust in the elderly and modifications to a TB vaccine, such as TLR2 ligand-based adjuvants, may help increase immune responses to a protective level.
Highlights
Latent tuberculosis infection (LTBI) has substantially declined in the developed world; reactivation of disease is prevalent among the aging population [1]
We demonstrate the feasibility of inducing targeted protective immunity through vaccination; this method could be applied to nursing home residents to help protect against infection with Mycobacterium tuberculosis (Mtb) and reactivation of LTBI
Surface levels of TLR2, TLR4, and CD36 were high on circulating B cells in the elderly subjects compared to previously published data on cells from adult, non-elderly populations [29]
Summary
Latent tuberculosis infection (LTBI) has substantially declined in the developed world; reactivation of disease is prevalent among the aging population [1]. Tuberculosis (TB) in the elderly is thought to be primarily attributed to reactivation of LTBI; enhanced transmission within the nursing home setting has been reported [2]. Tuberculosis rates in the USA are highest among nursing home or long term care facility populations [3]. Increasing rates of reactivation are facilitated by high prevalence in older adults with co-morbidities associated with progression to TB (e.g. chronic renal failure, poorly controlled diabetes) coupled with a higher proportion of the population living to an older age and being cared for in longterm care facilities [4]. Our recent report demonstrates that a discordance between TST and other diagnostics may add to the risk of transmission in nursing homes [10]
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