Scientists have identified a mechanism that helps explain why tuberculosis (TB) remains highly infectious in humans and animals. The research, published in Science Immunology, shows that the bacterium responsible for TB, Mycobacterium tuberculosis (MTB), exploits a component of the immune system called Dectin-1 to survive within host cells.
Tuberculosis continues to be one of the most lethal bacterial infections globally, causing approximately 1.5 million deaths each year. The disease is caused by MTB, which infects individuals when inhaled and subsequently taken up by immune cells such as macrophages. These cells use receptors on their surface to detect microbes and initiate immune responses; Dectin-1 is one such receptor known primarily for its role in defending against fungal infections.
The international study was co-led by the University of Exeter with contributions from Osaka University, the University of Cape Town, and the Francis Crick Institute. Researchers found that instead of protecting against infection as it does during fungal invasions, Dectin-1 actually aids MTB survival by triggering cellular responses favorable to the bacteria.
Dr. Max Gutierrez from the Francis Crick Institute said: "TB is a major killer worldwide, yet we still know very little about how it is so effective at causing infections, in both humans and in animals. 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."
The team demonstrated that when Dectin-1 was absent in human and mouse cells, these cells were better able to control MTB infection. Mice lacking Dectin-1 showed increased resistance to TB.
Further investigation revealed that MTB produces a molecule called alpha-glucan specifically to target Dectin-1 and induce immune cell responses that are harmful rather than protective.
Professor Sho Yamasaki from Osaka University commented: "Our results are surprising, because Dectin-1 is a key part of the body's defence system to protect against fungal infections, yet we've shown it's detrimental for MTB infections and actually promotes bacterial survival."
Associate Professor Claire Hoving from UCT added: "This research is a true international collaboration, with each institution bringing a distinct area of expertise. It's a fantastic example of the global partnerships required to tackle some of the greatest health challenges of our time."
Professor Gordon Brown from the University of Exeter's MRC Centre for Medical Mycology noted potential future applications: "This discovery is the first step – and opens the door to exciting new prospects including, for example, if we could knock out this receptor in cattle to make them more resistant to infection."
The study provides new insight into how TB evades immune defenses and suggests possible directions for developing strategies or treatments aimed at making hosts less susceptible to infection.
