Tuberculosis (TB) is still one of the biggest infection killers in the world. Multiple drug resistant (MDR) TB has become a global health emergency, an emerging European crisis and a major Irish health problem. Many challenges remain in the global battle against this disease, including a clinical need for effective treatments for MDR-TB.
Now, a research team from Trinity College, based at the Trinity Translational Medical Institute (TTMI) on St., is offering their own immune response to help them recover from TB.
The research team previously found that human immune cells change their energy consumption when infected. This change leads to the formation of lactate, which was previously considered a metabolic waste product. New work by the team has shown that lactate can affect cells in the lung environment to support immune defenses against infection while limiting collateral damage to the delicate lungs from excessive inflammation. Their study will be published today in the leading journal Frontiers in Immunology (Wednesday, October 6, 2021).
The research team is based in Professor Joseph Keane’s TB Immunology Laboratory at TTMI.
Dr. Cilian Ó Maoldomhnaigh conducted this research as part of a PhD project funded by the National Children’s Research Center and the Royal City of Dublin Hospital Trust.
He said, “Lactate has an immediate and remarkable effect on the metabolic function of human immune cells, reducing their ability to change their metabolism in response to subsequent infection. This has the effect of reducing inflammation, which can lead to damage in the lungs. We also found that lactate can aid a cell’s waste disposal processes so that it can effectively clear the infection. “
This waste disposal process, known as “autophagy,” also plays a role in a variety of other disease conditions such as Crohn’s disease, cancer, and heart disease, suggesting that lactate may have therapeutic potential in many disease situations.
The lead author of the article, Dr. Sharee Basdeo, Clinical Medicine, TTMI, is excited about the impact this work could have.
She said, “Our data suggests that aerosolized lactate released into the lungs may have the potential for host-directed therapy for people battling deadly pneumonia such as TB and COVID-19, which involve the lung tissue is destroyed due to uncontrolled prophylaxis. Inflammatory response. “
The paper: Lactate changes the metabolism in human macrophages and improves their ability to kill Mycobacterium tuberculosis can be viewed HERE.
Reference: Maoldomhnaigh C, Cox DJ, Phelan JJ, et al. Lactate changes the metabolism in human macrophages and improves their ability to kill Mycobacterium tuberculosis. Front. Immunol. 2021; 12: 4104. do: 10.3389 / fimmu.2021.663695
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