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angle-left Beyond Killing Tuberculosis

How can we tolerate an infection without eliminating a pathogen?

May 11, 2018

Historically, our view of host defense against infection was that we must eliminate pathogens to eradicate disease. However, this perspective has recently been challenged as scientists have taken a lesson from plant biologists about an ancient strategy involving the ability to “tolerate” rather than “resist” infection to maintain health. This concept, referred to as “disease tolerance”, provides an opportunity to develop new strategies that mitigate the consequences of infection.

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 trying 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.

Dr. Divangahi’s team found that rather than fighting to resist the pathogen, the body’s tolerance to 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.

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