Abstract
“Infection resisters” are broadly defined as individuals who despite significant exposure to Mycobacterium tuberculosis remain persistently unreactive to conventional detection assays, suggesting that they remain uninfected or rapidly clear their infection early on following exposure. In this review, we highlight recent studies that point to underlying host immune mechanisms that could mediate this natural resistance. We also illustrate some additional avenues that are likely to be differently modulated in resisters and possess the potential to be targeted, ranging from early mycobacterial sensing leading up to subsequent killing. Emerging research in this area can be harnessed to provide valuable insights into the development of novel therapeutic and vaccine strategies against M. tuberculosis.
Highlights
Tuberculosis (TB) is the leading cause of death from a single infectious agent, Mycobacterium tuberculosis[1]
23% of the world’s population is estimated to have a latent TB infection (LTBI), and 5 to 10% are at risk for progressing to active TB disease over the course of their lifetime[3,4,5], propagating the cycle of transmission
The common tests for TB screening include the tuberculin skin test (TST) and the blood test interferon gamma release assay (IGRA), which test for prior exposure to mycobacterial protein antigens
Summary
Tuberculosis (TB) is the leading cause of death from a single infectious agent, Mycobacterium tuberculosis[1]. Alternative mechanisms such as innatelike B1 cell mediated, T cell–independent responses[92,93] are yet to be investigated Such innate responses in resisters might be directed predominantly against non-protein mycobacterial antigens[94], possibly circumventing the development of the classic CD4+ T cell–mediated IFN-γ response, providing a reasonable explanation for persistent TST/IGRA negativity observed in these individuals. Our group reported that the transmissibility of strains belonging to the same lineage depends on their interaction with the host immune system leading to different trajectories in bacterial growth and in the development of disease pathology in the C3HeB/FeJ mouse model[115] This indicates that the role of immune variation in the host and the pathogen strain variation together may contribute to the infection-resistant and -susceptible phenotype in individuals exposed to M. tuberculosis.
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