Genetic resistance to Mycobacterium Tuberculosis infection and disease
Date
2018-09
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers Media
Abstract
Natural history studies of tuberculosis (TB) have revealed a spectrum of clinical outcomes
after exposure to Mycobacterium tuberculosis, the cause of TB. Not all individuals
exposed to the bacteriumwill become diseased and depending on the infection pressure,
many will remain infection-free. Intriguingly, complete resistance to infection is observed
in some individuals (termed resisters) after intense, continuing M. tuberculosis exposure.
After successful infection, the majority of individuals will develop latent TB infection
(LTBI). This infection state is currently (and perhaps imperfectly) defined by the presence
of a positive tuberculin skin test (TST) and/or interferon gamma release assay (IGRA),
but no detectable clinical disease symptoms. The majority of healthy individuals with
LTBI are resistant to clinical TB, indicating that infection is remarkably well-contained in
these non-progressors. The remaining 5–15% of LTBI positive individuals will progress to
active TB. Epidemiological investigations have indicated that the host genetic component
contributes to these infection and disease phenotypes, influencing both susceptibility and
resistance. Elucidating these genetic correlates is therefore a priority as it may translate
to new interventions to prevent, diagnose or treat TB. The most successful approaches
in resistance/susceptibility investigation have focused on specific infection and disease
phenotypes and the resister phenotype may hold the key to the discovery of actionable
genetic variants in TB infection and disease. This review will not only discuss lessons
from epidemiological studies, but will also focus on the contribution of epidemiology and
functional genetics to human genetic resistance to M. tuberculosis infection and disease.
Description
CITATION: Möller, M. et al. 2018. Genetic resistance to Mycobacterium tuberculosis infection and disease. Frontier in Immunology, 9:2219, 1-13. doi:10.3389/fimmu.2018.02219.
The original publication is available from https://www.frontiersin.org/journals/immunology#
The original publication is available from https://www.frontiersin.org/journals/immunology#
Keywords
tuberculosis, host genetics, resistance, resisters, susceptibility
Citation
Möller, M. Kinnear, C.J., Orlova, M., Kroon, E.E., Van Helden, P.D., Schurr, E. & Hoal, E.G. 2018. Genetic resistance to Mycobacterium tuberculosis infection and disease. Frontier in Immunology, 9:2219,1-13. doi:10.3389/fimmu.2018.02219.