The Francis Crick Institute
Anne O’Garra is an Associate Research Director, Senior Group Leader, Laboratory of Immunoregulation and Infection, at The Francis Crick Institute, London. After her Ph.D. at the MRC National Institute for Medical Research (NIMR), London, in microbial biochemistry, then as a Postdoctoral Fellow worked on cytokines and the immune response. At the DNAX Research Institute (now Merck), California, USA (1987 – 2001), as an independent Group Leader 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, showing that microbial products stimulate the production of IL-12 and IL-18 to direct Th1 responses and the production of IFN-, critical for eradication if intracellular pathogens. In turn, she showed IL-10 as a feedback regulator to inhibit damage to the host, conversely contributing in other contexts to chronic infections. O’Garra demonstrated a transcriptional signature of active tuberculosis dominated by type I interferon inducible genes, which she has shown contributes to chronic disease in part by induction of the suppressive cytokine IL-10 and inhibition of IL-12. She demonstrated that IL-10 can exacerbate TB in experimental models. More recently her lab and collaborators have published a reduced blood signature of active TB which does not detect other lung diseases. This signature was detected early after infection, transiently in a proportion of TB contacts who remained healthy, but stably expressed in contacts of TB patients who progressed to active TB.