A pioneering study by scientists at UCL discovered the presence of a harmful inflammatory protein in patients with symptomatic tuberculosis (TB).
Researchers say that by targeting the cytokine IL-17, a component naturally produced by the immune system in response to infection, the excessive and damaging lung inflammation caused by tuberculosis can be significantly reduced to help speed patient recovery. .
Tuberculosis is an infection caused by the bacteria Mycobacterium tuberculosis and is the leading cause of death from infection worldwide. The World Health Organization estimates that 1.4 million people died from tuberculosis worldwide in 2019.
Explaining the experimental study, lead author Dr Gabriele Pollara (Infection and Immunity Division, UCL) said: “For most people, the body’s immune response to TB is a vital defense strategy. to contain the infection, but when the disease develops, it can worsen symptoms, cause lung damage and help spread the infection to others.
“For some time, we’ve thought that the body’s own immune response to TB might actually cause more tissue damage and help the infection spread – but we didn’t know how that happened.
“In this study, we found that in patients with active TB, the immune system could respond pathologically (causing damage), and that this immune response was not present in patients with latent TB, who controlled the infection.
As part of the study, published in Scientific translational medicine, medical centers in the UK, South Africa and Peru have recruited patients to have a tuberculin skin test (TST), which involves injecting a small amount of fluid (called tuberculin) into the skin on the lower part of the arm. Raised skin or swelling, detected 48 hours later, indicates a positive test.
Subsequent testing confirmed that 48 of those recruited had symptomatic tuberculosis and 191 people had asymptomatic / latent tuberculosis. Genome-wide transcriptional profiling of TST biopsies was then performed to perform detailed measurements of the immune response.
The researchers found that samples from patients with symptomatic tuberculosis exhibited increased activity of the cytokine IL-17, which is an immune response known to cause tissue damage in other inflammatory conditions.
NIHR clinical lecturer Dr Pollara added: “This new research has identified for the first time the nature of these potentially harmful immune pathways. We show that a specific immune pathway, the cytokine IL-17, is present exclusively in the immune response of patients with tuberculosis, but not those who never develop symptoms.
“This is a fascinating discovery because IL-17 cytokine responses cause disease and tissue damage in other inflammatory conditions, such as psoriasis and ankylosing spondylitis. In both conditions, drugs that block the IL-17 pathway are very effective in improving symptoms in patients, and our results therefore indicate that these same drugs may also be of benefit in the treatment of patients with tuberculosis. “
For more than 50 years, the treatment of tuberculosis has relied mainly on antibiotics which kill bacteria. Although effective, this strategy has many challenges; treatment involves taking four antibiotics and lasts for at least six months, and its effectiveness is increasingly called into question by increasing rates of antibiotic resistance. Therefore, the development of new approaches to treat tuberculosis is an urgent global research priority.
Lead author Professor Mahdad Noursadeghi (Infection and Immunity Division, UCL) said: “Our work has the potential to radically change the management of TB patients, providing a rationale for targeting specific immune components, alongside the conventional use of antibiotics.
“We predict that this would speed up clinical recovery, interrupt transmission between individuals and reduce antibiotic treatment time. More broadly, these results open the door to an exciting new frontier in the treatment of infectious diseases.
“Understanding the immune responses to infections that are harmful justifies the use of targeted ‘host-directed’ drugs that complement the action of antibiotics. In turn, this strategy has the potential to limit the severity of the disease, shorten antibiotic cycles and therefore lessen the effects of antibiotics. increasing resistance to antibiotics around the world. “
The researchers aim to design a clinical trial to test whether drugs targeting the cytokine IL-17 in patients with symptomatic tuberculosis reduce symptoms and improve patient outcomes.
This work was supported by grants from the Wellcome Trust, the Medical Research Council, the Academy of Medical Sciences and the NIHR Biomedical Research Center at University College London Hospitals.