CD153, a molecule produced by the body, has been identified as a potential key to controlling Mycobacterium tuberculosis (Mtb) infection, in a new study published in Nature Microbiology.
The mechanisms of immune protection against Mtb are poorly understood, and the new study reveals that CD153 is critical to controlling the infection.
In a collaborative effort, researchers from institutions in the United States, South Africa, and the United Kingdom investigated the role of CD153 in mice and rhesus macaques, then corroborated their discovery in human patients.
First, the team showed that mice without CD153 were more susceptible to Mtb infection than unmodified animals. The team then investigated the role of CD153 in rhesus macaques, a non-human primate model of TB that more closely mimics human disease. Animals with more CD153-expressing immune cells in their lungs had fewer Mtb bacteria, confirming the molecule’s protective role.
To translate these findings to human disease, co-authors Catherine Riou and Elsa du Bruyn of the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) assessed CD153 expression in people with either active or latent Mtb infection. People with latent disease – which when the immune system keeps the infection in check – had higher expression of CD153 in the relevant immune cells, offering further evidence that CD153 helps to control Mtb.
Professor Robert J Wilkinson, Group Leader at the Francis Crick Institute and Director of CIDRI-Africa, said: "The quest for factors that protect people against tuberculosis has been difficult and long, though critical for vaccine design and evaluation. Whilst all the mechanisms remain to be elucidated, this work presents a series of observations coherent across species that CD153 plays an important role in tuberculosis and these findings have attracted considerable interest worldwide."
Overall, these data suggest that CD153 may be a key component in the control of Mtb infection. Moreover, this molecule may be a useful biomarker of protection and could possibly be used to evaluate the efficacy of new TB vaccines.
“These findings are really exciting and may help in the quest for correlates of protection against tuberculosis and the development of much-needed diagnostic tools. Further studies are now needed to investigate the mechanism of action of CD153,” commented Dr Riou.
Dr Pete Gardner, from Wellcome’s Infection and Immunobiology team. “We only have a partial understanding of how our bodies fight TB, which is a real barrier to developing new and more effective vaccines. This important study identifies a critical role for a certain type of immune cell, which can bring about a protective response to the disease in the lungs. This information is vital to informing the design of future vaccines that could help to tackle TB which infects over ten million people around the world each year.”
As many as two billion people are infected with Mtb, but most will never go on to develop active TB disease because their immune systems are able to control the infection. They may never experience symptoms and do not transmit the bacterium. However, 10% will progress to active TB, and will experience potentially severe and life-threatening illness. In South Africa alone, more than 100,000 people died due to active TB in 2016.