A breakthrough in tuberculosis research
Often causing no symptoms in carriers of the disease, worldwide tuberculosis (TB) infects eight to ten million people every year, kills two million, and it is highly contagious as it is spread through coughing and sneezing. 鈥淚t鈥檚 a global health disaster waiting to happen, even here in Canada, but this new paradigm in TB research may offer an immediate opportunity to improve vaccination and treatment initiatives,鈥 explains Dr. Maziar Divangahi of 捆绑SM社区 University and of the Research Institute of the 捆绑SM社区 Health Centre.
The ability of TB bacteria to persist in individuals with apparently normal immune systems implies that they have developed strategies to avoid, evade, and even subvert immunity. The bacteria mainly enter the body through inhalation into the respiratory tract. Alveolar macrophages, a type of white blood cell residing in our lungs, initially recognize the bacteria and engulf them. This process is one of our immune system鈥檚 defense mechanisms. However, TB has evolved into a parasite that can survive and replicate inside the macrophages until they burst out, spreading the infection.
The way infected macrophages die is a determining factor in the development of immunity to TB. Macrophages can induce apoptosis, a type of cell death which keeps their membrane intact, trapping and reducing bacterial viability. However, TB bacteria induce another type of cell death called necrosis. Necrosis causes cell death by disrupting the cell membranes, which enables the bacteria to escape the cell. It may help to visualize a box with broken walls.
The key to the fate of the macrophages is the balance between two kinds of eicosanoids. Eicosanoids are molecules that contribute to the control of our immune system. The genetic code of TB bacteria enables it to tip this balance in favor of necrosis, and human genetic analysis revealed that modification in eicosanoids production is associated with susceptibility or resistance to TB. Fortunately, drugs that target the production of eicosanoids are already in use for treating other inflammatory diseases, such as rheumatoid arthritis.
鈥淭he next steps will be to see exactly how these drugs can be used to treat TB,鈥 said Divangahi. The research received funding from the Fonds de la Recherche en Sant茅 du Qu茅bec and was published in Nature Immunology. Divangahi is affiliated with the Departments of Medicine and Microbiology/Immunology of 捆绑SM社区鈥檚 Faculty of Medicine, with the Research Institute of the 捆绑SM社区 Health Centre, and with the Meakins-Christie Laboratory.
Web: Dr. Divangahi鈥檚 Homepage at 捆绑SM社区鈥檚 Meakins-Christie Laboratories website:
Also of interest: 捆绑SM社区 researchers publish an editorial in Expert Reviews of Respiratory Medicine about the increased risk of a TB epidemic following the earthquake in Haiti :