Researchers have found that rather than fighting to resist the pathogen, the body's tolerance to Mycobacterium tuberculosis, or Mtb is the key mechanism for preventing the spread of the infection. More surprisingly, they found that having excessive levels of T cells, which are known as soldiers of our immune system, could cause more harm than good. Since the discovery of Mycobacterium tuberculosis, or Mtb, (the bacteria causing TB) over a century ago, great progress has been made in defining strategies that facilitate elimination of the bacteria. For instance, the discovery of antibiotics was a major breakthrough in the treatment of active TB. However, greater than 90 per cent of TB-infected individuals tolerate the bacteria without any treatment. Dr. Maziar Divangahi, a pulmonary immunologist at the Research Institute of the McGill University Health Centre (RI-MUHC) and a professor of Medicine at McGill University in Montreal, has been try-ing to explain why the vast majority of people infected with Mtb can tolerate the infection without developing disease. Clinicians refer to this condition as "latent tuberculosis", and it affects a quarter of the global population. "TB is a perfect example of disease tolerance," says Dr. Divangahi who is also the associate director of the Translational Research in Respiratory Diseases Program at the RI-MUHC and a member of the McGill International TB Centre.
‘Tuberculosis is a perfect example of disease tolerance. Disease tolerance is an ancient strategy involving the ability to "tolerate" rather than "resist" infection to maintain health.’
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"We always thought that having more T cells would provide better protection against TB. Instead, we found that it could imbalance disease tolerance causing extensive tissue damage and ultimately killing the host," says Dr. Divangahi, lead author of the study published today in Science Immunology, who is the also the associate director of the Meakins-Christie Laboratories. Disease tolerance versus host resistance
Our body's defense system is divided into two arms: one is resistance, which aims to eliminate the pathogen, while the other is tolerance, which is designed to control the tissue damage caused by the infection. "While disease tolerance is an established field of research in simple organisms such as plants, our un-derstanding of this host defense strategy in humans is very limited," says Dr. Divangahi.
Although, immunologists and vaccinologists have made progress in the study of host resistance to infectious diseases, little is known about the mechanisms of disease tolerance in humans.
A key protein in disease tolerance
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Giving the widespread drug resistance to various Mtb strains the limited pipeline of effective antibiotics and the lack of an efficient vaccine, alternative approaches to treat TB are urgent. "If we could understand the mechanisms of 'natural immunity' that controls TB in 90-95 per cent of infected individuals," says Dr. Divangahi,"we will able to design a novel therapy or vaccine to substantially reduce the world wide burden of this ancient disease."
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