£3.5M Awarded to Investigate How Puberty Affects Immune Responses to Mycobacterium Tuberculosis
21 November 2025
The study is funded by Wellcome and will help uncover insights about adolescent tuberculosis.
Led by Imperial’s Professor James Seddon, DEFIANT is a six-year research study in partnership with Stellenbosch University and University of Cape Town (UCT) in South Africa. The project aims to investigate the underlying mechanisms of tuberculosis (TB) in adolescence and explore how puberty influences the immune response to Mycobacterium tuberculosis in both the blood and sputum.
The goal for scientists is to identify risk factors that predict which adolescents are most likely to experience complications from TB, as well as the biological processes involved. Understanding this could build the foundation for new therapies designed to interrupt these damaging inflammatory pathways and improve outcomes for young people affected by TB worldwide.
Professor James Seddon said, “We know very little about how the immune system changes during puberty and how this might impact on responses to the TB bacteria. We know that the risk of developing severe forms of TB increases dramatically during adolescence, with increasing lung damage and morbidity. A better understanding of why and how this happens could make a substantial difference to this vulnerable group.”
The problem of tuberculosis in adolescence
Tuberculosis remains a significant global health challenge and evidence shows that there is an increasing incidence of TB during adolescence (ages 10-19 years), when rates of disease rise due to a combination of biological and social factors.
Over a million adolescents worldwide develop TB, yet research focused on this age group is limited. The increase in infectious TB and post-TB complications could be due to hormonal changes associated with puberty, as well as external influences such as nutrition and social networks.
To explore the immunological changes that occur during adolescence, the DEFIANT study will analyse samples from 100 adolescents with pulmonary TB – a form of disease which primarily affects the lungs – alongside 200 healthy controls. Researchers will investigate how pubertal stage relates to inflammatory responses in the blood and sputum, and in turn how this drives disease severity. Severity will be assessed using PET/CT, a form of imaging that not only assesses the anatomy of the lungs but also gives important information about inflammation and metabolism.
The study is scheduled to begin in early 2026.
International collaborations
Professor van der Zalm, a co-applicant on the study from Stellenbosch University and a world expert on post-TB lung disease in children and adolescents, said: “I am really excited to begin the DEFIANT study. Not only is this a wonderful collaboration between Imperial, Stellenbosch and UCT, but for the first time, we hope to understand why adolescents develop such severe TB complications and so can begin to identify novel drugs that might provide benefit.”
Source: Imperial College London
