Anne O’Garra group

Regulation of the immune response in infectious disease

The immune system is effective in eradicating pathogens via many mechanisms, including soluble mediators called cytokines. Immune cells can produce different cytokines to control infection, but can cause host damage if uncontrolled. We are researching the molecular mechanisms underlying the development and function of discrete subsets of immune cells that produce different cytokines protective against pathogens, and the induction and function of a regulatory cytokine, IL-10. (Figure 1) We use diverse tools to study the mechanisms of IL-10 gene regulation in macrophages, dendritic cells and T cells, and the consequences of IL-10 action in mouse models of infectious diseases, with strong emphasis on tuberculosis (TB) caused by Mycobacterium tuberculosis.

TB is a major cause global cause of morbidity and mortality. Using a systems biology approach we identified a robust blood transcriptional interferon-inducible neutrophil-driven signature in human TB, and longitudinal analysis revealed that this signature disappears during successful treatment (Figure 2). Based on these findings and continued studies in human disease and in cellular and in vivo experimental models (Figure 2), we are continuing to identify immune mechanisms of protection or pathogenesis important for disease control in tuberculosis and other bacterial infections.

Figure 1: Regulation of IL-10 production in immune cells

Figure 1: Regulation of IL-10 production in immune cells

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Figure 2: Experimental models

Figure 2: Experimental models

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O’Garra group

Dr Anne O’Garra

Anne O’Garra
aogarra@nimr.mrc.ac.uk

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