How Tuberculosis Targets the Immune System

Although ancient, TB is still the world’s deadliest infectious disease. It is rampant in Africa, and the growing problem of antibiotic resistance is posing a significant threat worldwide.

In a study published yesterday in Cell Reports, Trinity College Dublin scientists made two discoveries concerning tuberculosis: (1) how TB puts the brakes on our immune engines and (2) how we can kick-start those engines back into gear. The results give hope for improved treatment options for TB.

Part of TB’s success as a pathogen is because of its ability to infect the cells of our immune system, which are normally tasked with responding to the infection. It infects the lung macrophage cells and then manipulates them to its own benefit, creating a safe “home” for itself. The researchers have been examining how these lung macrophage immune cells fuel the fight against infection.

In the current study, the researchers found that persistent infection of these macrophages with TB puts the brakes on the glucose-fuelled engine. This essentially shuts down our natural response to infection, which allows the bacteria to hide out unperturbed—sometimes for years.

Specifically, the team found that the bacteria promote a small RNA molecule microRNA-21. This RNA targets and removes key enzymes that act as pumps in our immune engines to commit glucose to promote the anti-bacterial response, allowing the bacteria to escape and thrive.

“We found that when TB-infected cells are treated with a key ‘Interferon gamma protein signal,’ which is normally produced following vaccination, they will remove this microRNA to effectively relieve the brake and restore our normal immune response,” says senior author Frederick Sheedy. “What is particularly promising from a societal impact perspective is that as well as increasing our knowledge of how TB corrupts our normal immune response to infection, our identification of the microRNA-21 means that scientists should be able to develop improved immunotherapies or vaccine strategies to help in the fight against TB infection.”