june 2016

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TB Immunology Group Discover Mechanisms for Susceptibility

The TCD St. James’s TB immunology group has recently published in Cell on the mechanisms that drive the colliding epidemics of tuberculosis and smoking. The research team, led by Dr. Mary O’Sullivan and Dr. Seónadh O’Leary, discovered how cigarette smoking prevents immune cells from moving towards TB bacteria which prevents the lungs defence system dealing with infection. TB is an infectious disease that kills 4000 people every day and smoking is the biggest driver of this global epidemic.  The TB Immunology group is led by Prof Joseph Keane.

The research was done in collaboration with Prof Lalita Ramakrishnan and her team in Cambridge, UK, who work with a zebra fish model of tuberculosis. They had demonstrated that macrophages which were unable to degrade engulfed cellular debris carry a high burden of vacuoles and failed to migrate properly in response to bacterial infection. Drs O’Leary and O’Sullivan extended these findings to the human model of tuberculosis and sought to see how this might apply specifically to the behaviour of macrophages from smokers; which also have a high vacuole burden, because of their inability to get rid of cigarette smoke derived material.  They showed that migration of smokers’ macrophages to M. tuberculosis was impaired and found that the migration impairment was specific to the vacuolated subset of macrophages. Reviewers of the paper thought the extension of zebra fish findings to cigarette smoking is an important advance in the field. This discovery can potentially have an immediate impact within the field of TB as it uncovers a mechanism by which smoking may contribute to TB susceptibility.

The Irish research was funded by the Health Research Board and the Royal City of Dublin Hospital Trust.

Pictured (left to right): Professor Joseph Keane, Dr Seónadh O’Leary and Dr Mary O’Sullivan.


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