School of Infection & Immunity

Dr Anne O'Garra

Title: Transcriptional signatures reveal the immune response underlying progression and pathogenesis in tuberculosis

Synopsis:

Most people infected with M. tuberculosis remain asymptomatic while only a fraction progress to active TB, with 1.25 million deaths in 2023. We identified a human TB blood transcriptional type I IFN-dominated signature, which was diminished upon treatment, correlating with lung radiological extent of disease and absent in most exposed asymptomatic individuals. M. tuberculosis infected susceptible mice displayed a blood signature resembling the human type I IFN-dominated TB signature, and blockade of type I IFN receptor signalling reduced neutrophil activation, lung pathology and infection burden confirming a role for type I IFN in TB pathogenesis. More recently we revealed the early responses in airways of human TB contacts and recapitulated these signatures and function in TB-resistant and TB-susceptible mouse models, shedding light on potential mechanisms for infection control or progression to TB disease. Anne O’Garra and this work was funded by the MRC, UK; The Dana Foundation; Institut Merieux; ERC-2011-AdG, 294682-TB-PATH; Bioaster/Biomerieux; La Caixa Foundation; The Wellcome Trust and The Francis Crick Institute, London.  Anne O’Garra thanks all who have contributed and/or collaborated in this work throughout the years.

Bio:

Anne O’Garra is a Principal Group Leader, heading the Laboratory of Immunoregulation and Infection, at The Francis Crick Institute, London. She obtained her PhD at the MRC National Institute for Medical Research (NIMR), London, in microbial biochemistry then changed fields in her Postdoctoral Fellowship to work on cytokines and the immune response in the Division of Immunology, NIMR.  As an independent Group Leader at the DNAX Research Institute (now Merck), California, USA (1987 – 2001) she directed her laboratory in defining key functions and mechanisms for cytokine expression and function in the immune response. She identified IL-10 as a major regulator of immune responses by its effects on macrophages and dendritic cells at the level of antigen presentation and cytokine production. She also showed that microbial products stimulate the production of IL-12 and IL-18 to direct Th1 responses and the production of IFN-g, critical for eradication if intracellular pathogens. In turn, she showed IL-10 as a feedback regulator to inhibit damage to the host, but conversely contributing in other contexts to chronic infections. She was recruited back to the NIMR in 2001, and formed the new Division of Immunoregulation, NIMR, (2001), to interface the divisions of immunology and infectious diseases. She continued her research on cytokines and immunoregulation, now additionally with an additional focus on the immune response in tuberculosis (TB), in both mouse models and human disease, identifying type I interferon as a key mediator of TB pathogenesis.

First published: 19 May 2026

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