Scientists at James Cook University have uncovered new insights into how the body contains latent tuberculosis, using a cutting-edge technique that allows researchers to map exactly where immune cells and bacteria interact inside tissues.
The research, published in Nature Communications, was supported by a grant from the United States National Institutes of Health and has also enabled early testing of a new tuberculosis vaccine candidate to help prevent the disease from reactivating.
Around two billion people worldwide are infected with latent tuberculosis, an inactive form of the disease that causes no symptoms and is not contagious. However, in five to ten per cent of cases, the dormant bacteria can reactivate and develop into life-threatening illness.
Reactivation is more likely when the immune system is weakened, including in older people and those with conditions such as diabetes or HIV.
James Cook University's Professor Andreas Kupz said understanding why this happens remains a critical challenge.
"Studying latent tuberculosis infections is difficult because Mycobacterium tuberculosis only infects humans, so most animal models don't really show this type of latent infection," he said.
To overcome this, Professor Kupz and Dr Socorro Miranda-Hernandez developed a model that mimics infection beyond the lungs.
"There is evidence that the latent infection in humans doesn't actually occur in the lung, even though the original infection happens there," Professor Kupz said.
"Instead, the tuberculosis bacteria may reside in lymphatic organs such as lymph nodes or the bone marrow. This type of lymphatic infection can be simulated in a contained tuberculosis model."
Central to the breakthrough is a technology known as spatial transcriptomics, which allows scientists to study whole tissues rather than isolated cells.
"Until about five or six years ago, when studying the immune system, a lot of what we had to do was based on isolated immune cells," Professor Kupz said.
"Now, we can look at entire tissue as a whole, and we can actually find which cells are neighbouring other cells," he said.
"We can spot exactly where the latent tuberculosis bacteria are. Spatial transcriptomics allows us to investigate what actually happens in those lymph nodes when the bacteria are either contained or when they can escape from containment."
Using this approach, the team identified a key role for CD8+ T cells in controlling the infection.
"Thanks to our findings, we now know what the CD8+ T cells do in the lymph nodes, and how they do it spatially," Professor Kupz said.
"But we don't know exactly how they kill the bacteria, or if they simply provide a barrier."
"If we get the appropriate funding, we are planning to push this research to the next level," he said.
"Over the next five years, we want to work out how these cells actually mediate containment, because that's still the missing link — to explain how latent tuberculosis reactivates."
