Professor Anne O'Garra works on signals that control the immune system, aiming to understand how it responds to diseases (such as tuberculosis, or ‘TB’, a disease caused by Mycobacterium tuberculosis ) and what goes wrong when the response damages healthy cells.
Our immune systems use many mechanisms to protect us from infection, including messenger molecules called ‘cytokines’. Cytokines help to direct immune cells, telling them where and when to attack. Immune cells can produce different cytokines in response to infection but uncontrolled responses can damage healthy cells and cause inflammation and disease.
In my laboratory we study how a regulatory cytokine called IL-10 is produced and how it works. IL-10 helps to turn down the immune response, thereby preventing damage to healthy cells. In some infections IL-10 can contribute to chronic disease by down-regulating protective cytokines and allowing pathogens to persist.
IL-10 is produced by many immune cells, including macrophages and T helper cells which tell other immune cells what to do. We look at how IL-10 is regulated in these cells as compared to the protective cytokines, and the effects of perturbing the molecular regulation of IL-10 at a cellular level and in mouse models of infectious diseases.
We additionally research the immune response in tuberculosis, that kills more than a million people every year. In 2010, we identified a gene signature dominated by type I interferon inducible genes in the bloodstream of people with TB, which disappears during successful treatment. We’re also studying the regulation and function of type I IFNs which exacerbate bacterial infections, in part by inducing IL-10.
Based on these findings and continued studies in humans, cells and mice, we continue to identify immune mechanisms of protection or pathogenesis important for disease control in TB and other bacterial infections.
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et al., 2021, Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis, Journal of Experimental Medicine, Vol:218, ISSN:0022-1007
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et al., 2020, Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis, Nature Communications, Vol:11