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Protecting children against Tuberculosis Infection

Dr Cilian Ó Maoldomhnaigh: Protecting children against Tuberculosis Infection

Cilian is a Paediatric Infectious Disease Consultant at CHI conducting research in collaboration with Professors Joseph Keane and Sharee Basdeo at the Trinity Translational Medical Institute. He was recently awarded a prestigious HRB Clinician Scientist Postdoctoral Fellowship to undertake the project “Targeting immunometabolism to protect children from Tuberculosis infection”.

Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). It predominantly affects the lungs with patients developing symptoms such as a cough, fever, and weight loss, but it can also affect other parts of the body, including the brain, kidneys, and spine. Unfortunately, TB continues to be a leading cause of child death worldwide.


Dr. Cilian Ó Maoldomhnaigh

“TB was the top global infectious killer in the last decade. Children are disproportionately affected by TB, with an increased risk of both getting the disease following exposure and of severe disease that spreads from the lungs causing issues such as meningitis. About 1 million children get sick with the disease and 250,000 children die from TB every year.
Dr. Cilian Ó Maoldomhnaigh explains.

Newborn babies are particularly susceptible to developing TB. As part of his PhD studies, Cilian studied how immune cells from newborns respond to TB bacteria and found that they have a weakened immune response compared to adults.

The most vulnerable time in life to TB infection is just after birth and I have previously shown that immune cells from newborn babies produce less inflammatory signals than adult immune cells when exposed to dead bugs” said Cilian.

With the rise of drug resistant strains of TB, the development of new treatments for TB is very important and improving how a child’s immune cells respond to TB bacteria is a potential therapeutic strategy.

Treatment for TB requires many months of multiple drugs and drug resistance is rising annually. Therapies that improve the host immune response are vitally needed” stated Cilian.

In his HRB postdoctoral fellowship, Cilian will study how immune cells from children respond to TB, with a focus on how immune cells use different energy pathways to kick into action and kill TB bacteria. He will use this knowledge to look at how the use of the immune cell’s energy pathways can be optimised to improve their ability to kill TB bacteria. This could contribute to the development of better treatments that help support the immune response to TB infection.

“Immune cells change the way that they use energy after they have been stimulated but I have shown that newborn immune cells do this differently to adult cells and that these pathways can be targeted to improve outcome. I have previously shown that interferon gamma (IFN-γ), an inflammatory signalling molecule, can improve immune function in newborn immune cells that have been stimulated with dead bugs. I have also shown that lactate can improve killing of TB in adult immune cells and alter the energy pathways that both adult and newborn immune cells use. I will examine the effect of lactate and IFN-γ on newborn cells infected with live, clinically relevant strains of TB.
Dr. Cilian Ó Maoldomhnaigh states.

This project continues Cilian’s long held interest in TB research and is very relevant to his clinical work at CHI.

“I have always been fascinated by TB and it was the focus of my PhD research. As a Consultant in the Rainbow Clinic which is the National Centre for Paediatric Infectious Disease and Immunology at Children’s Health Ireland, we are involved in the treatment of most of the children with active TB infection in the country and it is clear that new therapies are needed, particularly with the rising incidence of drug resistant strains of TB” said Cilian.

Read more about Cilian’s research

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