Publications and Further Research Outputs
- Jameson G, Walsh A, Woods R, Batten I, Murphy DM, Connolly SA, Duffin E, O'Gallchobhair O, Nadarajan P, O'Connell F, Gleeson LE, Keane J, Basdeo SA, Human tissue-resident NK cells in the lung have a higher glycolytic capacity than non-tissue-resident NK cells in the lung and blood., Proceedings of the National Academy of Sciences of the United States of America, 2024Journal Article, 2024
- Murphy, D.M., Cox, D.J., Connolly, S.A., Breen, E.P., Brugman, A.A.I., Phelan, J.J., Keane, J., Basdeo, S.A., Trained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine, Journal of Clinical Investigation, 133, (2), 2023Journal Article, 2023, DOI
- Gaffney E, Murphy D, Walsh A, Connolly S, Basdeo SA, Keane J, Phelan JJ, Defining the role of neutrophils in the lung during infection: Implications for tuberculosis disease., Frontiers in immunology, 2022Journal Article, 2022, DOI
Research Expertise
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TitleDefining the consequences of innate immune training on protective versus pathogenic T cell responses in patients with tuberculosis.SummaryTuberculosis (TB) ranks alongside HIV as the world's most deadly infectious disease, killing 1.5 million people every year. It is caused by the bacteria Mycobacterium tuberculosis (Mtb), which primarily infects people's lungs. Treating this disease is becoming more difficult due to antibiotic-resistant Mtb, therefore, scientists are developing ways to boost the immune system to kill Mtb more effectively. Two immune cells that play a prominent role in our ability to fight Mtb are alveolar macrophages (AM) and T cells. AM are the guardians of the lungs and encounter the bacteria first. They try to contain infection by eating and killing the bacteria, and then switching on T cells. However, Mtb can manipulate the AM and live inside it, causing TB disease. T cells are the generals of the immune system, helping to coordinate long term defence. However, in TB, these cells can be a double-edged sword; sometimes they can help clear the infection, but they can also cause collateral damage to the lungs. It was recently discovered that AM can be "trained" to increase their functions (similar to the way training improves an athlete's performance). This improves the AM's ability to kill bacteria. In addition, we have evidence to suggest this training will give clearer signals to the T cells, which will balance the immune response towards clearing the infection, rather than damaging the lungs. This project will compare different training regimens to see which best promotes the killing of Mtb and what affect the training has on T cell responses. By studying the different types of T cells that are activated during Mtb infection, we will determine which response may be harmful to the patient. By better understanding the human immune response during Mtb infection, we will be able to adjust it to help the patient recover from TB.Funding AgencyHealth Research BoardDate From01 March 2020Date To28 February 2025
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TitleDefining how innate immune function is impacted long term in people who have had active Tuberculosis.SummaryThe Problem Tuberculosis (TB) is a complex disease caused by a bacteria called Mycobacterium tuberculosis (Mtb) and claims the lives of 1.4 million people annually. When a person is exposed to Mtb, their immune response may clear the infection asymptomatically, contain it in a dormant state (called latent TB) or it can grow and replicate inside the macrophage causing active TB disease. The gap in our knowledge TB doesn't play by the rules of the immunity to infection. If you have previously had active TB you are more likely to get sick again with TB than someone who has never had it before and we don't know why. Our proposed solution Our research team study the innate immune response to Mtb and have established ways to therapeutically boost a patient's own immune system to fight off the bug. We think that Mtb may alter the function of the innate immune response long term in people who have previously had TB. This altered function is a bit like a scar that is left after an injury and we propose that this may be the reason why people who have had TB are more vulnerable to getting TB again. We want to define the status of innate immune cells in people who have had TB compared with healthy people in order to determine if their innate immune responses are reprogrammed by the infection. This will enable us to design a therapy aimed at protecting these vulnerable people from contracting TB again.Funding AgencyHealth Research BoardDate FromSeptember 2022Date ToMarch 2025
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TitleReprogramming systemic and tissue resident innate immunity post infection to inhibit autoinflammatory events and diseaseSummaryFunding AgencyEnterprise IrelandDate FromMarch 2023Date ToFebruary 2024
Recognition
- Nominated as Trinity's favorite Woman in Science 2023 (DU General Science Soc) March 2023
- Awarded Excellence in Research Supervision June 2023