New research reveals how tuberculosis hijacks the immune system

Scientists from the University of Cape Town have helped uncover a key reason why tuberculosis (TB) remains so effective at infecting humans and animals. The bacterium responsible is able to hijack part of the immune system designed to protect the body from disease.

The international study found that Mycobacterium tuberculosis (MTB) exploits an immune receptor known as Dectin-1 — normally crucial in fighting fungal infections, to survive and multiply inside host cells. The findings were published in Science Immunology.

Despite more than a century of research, TB remains one of the world’s deadliest bacterial infections, causing an estimated 1.5 million deaths each year.

TB infection begins when airborne bacteria are inhaled and engulfed by immune cells such as macrophages. These cells rely on surface receptors to recognise invading microbes and trigger protective immune responses. One such receptor, Dectin-1, is best known for its role in anti-fungal immunity.

However, the researchers found that MTB has evolved to turn this defence mechanism to its advantage.

The study showed that MTB targets Dectin-1 to drive immune responses that favour bacterial survival rather than clearance. When the Dectin-1 pathway was absent, both human and mouse cells were better able to control TB infection. Mice lacking the receptor were significantly more resistant to the disease.

“This research is a true international collaboration, with each institution bringing a distinct area of expertise,” said Associate Professor Claire Hoving, an associate member of UCT’s Institute of Infectious Disease and Molecular Medicine and the Wellcome Trust Centre for Infectious Disease Research in Africa.

“It’s a fantastic example of the global partnerships required to tackle some of the greatest health challenges of our time,” she said.

The team  which included scientists from UCT, the University of Exeter, Osaka University and the Francis Crick Institute also identified a unique bacterial molecule, alpha-glucan, which binds to Dectin-1 and triggers these harmful immune responses.

Dr Max Gutierrez, of the Francis Crick Institute, said TB’s ability to subvert immunity remains poorly understood despite its global impact.

“Our discovery of a new mechanism by which Mycobacterium tuberculosis is able to subvert host immunity is a key step in understanding the basis of susceptibility to TB,” he said.

Professor Sho Yamasaki, of Osaka University, said the findings were unexpected.

“Dectin-1 is a key part of the body’s defence system against fungal infections, yet we’ve shown it’s detrimental for MTB infections and actually promotes bacterial survival,” he said.

Professor Gordon Brown, of the University of Exeter’s MRC Centre for Medical Mycology, said the discovery could have far-reaching implications.

“This is the first step and opens the door to exciting new prospects — including the possibility of knocking out this receptor in cattle to make them more resistant to infection,” he said.

The study is titled Mycobacterial α-glucans hijack Dectin-1 to facilitate intracellular bacterial survival.

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