Researchers have identified distinct immune responses in the lungs that may determine whether individuals infected with Mycobacterium tuberculosis develop active disease or successfully control the infection. The findings, published in Nature Immunology, could lead to earlier identification of at-risk individuals and new treatment approaches.
Approximately a quarter of the global population is estimated to have been infected with tuberculosis (TB), yet only 5–10% develop active disease. Understanding what distinguishes those who control infection from those who progress to illness has been a longstanding research question.
Scientists at The Francis Crick Institute, collaborating with clinicians at University Hospitals of Leicester NHS Trust, analysed bronchoalveolar lavage samples from recent household contacts of people with pulmonary TB. Using bulk and single-cell RNA sequencing alongside flow cytometry, they examined which immune cells were present in the airways and their activity patterns.
In individuals who developed active TB, airways were dominated by neutrophils, with half of these cells showing activated type I interferon signalling genes. These neutrophils produced high levels of CXCL8, a molecule that recruits additional neutrophils, potentially creating a cycle of inflammation. T cells in these patients showed signs of exhaustion and cell death.
By contrast, individuals who controlled infection showed T cells that were neither highly activated nor exhausted. Instead, these cells expressed genes linked to regulation and a stem-like state, suggesting capacity for persistent, long-term response.
The researchers identified similar patterns in published data from non-human primates and previous mouse studies. Senior author Anne O’Garra noted that if these immune signatures can be identified early in infected individuals, it may become possible to predict who is at risk and develop targeted interventions to steer immune responses toward protection.
Source: Medical Xpress / The Francis Crick Institute (Nature Immunology, 2026)
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