By: Richard Liang 18’
Tuberculosis (TB) is a highly infectious disease that can remain dormant for many years. Currently, treatment options are limited by Mycobacterium tuberculosis’s ability evade the immune system and mutate into drug-resistant strains. Outbreaks are a more pressing concern in developing countries, where health care is less accessible. In a recent study led by Catherine Y. Cheng from the Singapore Immunology Network, a potential therapeutic target has been discovered that can be used to develop better treatments against tuberculosis.
Sirtuin 1 (SIRT1), a nictoinamide adenine dinucleotide dependent decaetylase, has been determined to be a key factor in the pathogenesis of tuberculosis. By performing a pairwise comparison of SIRT1 mRNA expression profiles in the peripheral blood of active TB patients, latent TB individuals and healthy individuals, it was determined that SIRT1 expression was down regulated to more than 50% in those infected with TB.
The same type of trend was observed when mice were infected with the disease. Mice were infected with TB and were then injected with an SIRT1 activator to determine whether SIRT1 activation would reduce the symptoms of TB. Light micrographs of their lung sections showed that the mice treated with the SIRT1 activators had much less inflammation in their lung tissue, compared to the control mice that had been left untreated. Further evidence came when mice that were SIRT1 knockouts demonstrated greater bacteria load than the Wild-Type mice, suggesting that the presence of SIRT1 impedes infection.
The results thus indicate that countering the down regulation of SIRT1 could potentially alleviate TB infections. However, the researchers stress that their results do not describe the relationship between SIRT1 and the adaptive immune response. Further experimentation with this therapeutic target should help researchers determine and increase the efficacy of this treatment for humans.
- Y. Cheng, et al., Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis. Science Immunology 2, (2017) DOI: 10.1126/sciimmunol.aaj1789
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