Anne O’Garra

Immunoregulation and Infection Laboratory

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.

Figure 1

Figure 1: Regulation of IL-10 production in immune cells. (Click to view larger image)

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 TB and other bacterial infections and the role of Type I interferons (IFNs) in exacerbation of bacterial infections.

Figure 2

Figure 2: Experimental models. (Click to view larger image)

Selected publications

Gabryšová L, Howes A, Saraiva M, O'Garra A. (2014) The regulation of IL-10 expression. Curr Top Microbiol Immunol.;380:157-90.

Saraiva, M; Christensen, JR; Veldhoen, M; Murphy, TL; Murphy, KM and O'Garra, A (2009) Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 31, 209-219

Berry, MPR; Graham, CM; McNab, FW; Xu, Z; Bloch, SAA; Oni, T; Wilkinson, KA; Banchereau, R; Skinner, J; Wilkinson, RJ; Quinn, C; Blankenship, D; Dhawan, R; Cush, JJ; Mejias, A; Ramilo, O; Kon, OM; Pascual, V; Banchereau, J; Chaussabel, D and O'Garra, A (2010) An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466, 973-977

O'Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MP. The immune response in tuberculosis. Annu Rev Immunol. 2013.31:475-527.

Blankley S, Berry MP, Graham CM, Bloom CI, Lipman M, O'Garra A. 2014. The application of transcriptional blood signatures to enhance our understanding of the host response to infection: the example of tuberculosis. Philos Trans R Soc Lond B Biol Sci;369(1645).

McNab FW, Ewbank J, Howes A, Moreira-Teixeira L, Martirosyan A, Ghilardi N, Saraiva M, O'Garra A. 2014. Type I IFN induces IL-10 production in an IL-27-independent manner and blocks responsiveness to IFN-g for production of IL-12 and bacterial killing in Mycobacterium tuberculosis-infected macrophages. J.Immunol. 193(7): 3600-12.

McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. Type I interferons in infectious disease Nat Rev Immunol. 2015 Jan 23;15(2):87-103

Anne O’Garra

anne.ogarra@crick.ac.uk
+44 (0)20 379 61547

  • Qualifications and History
  • 1983 PhD Microbiology MRC-NIMR, London, UK
  • 1984-1987 Post Doctoral Fellow Immunology MRC-NIMR, London, UK
  • 1987-1990 Post Doctoral Fellow Immunology DNAX Research Institute (now Merck), Palo Alto, California, USA.
  • 1991-2001 - Group Leader/Principal Scientist, DNAX Research Institute, California, USA.
  • 2001 Group Leader and Head of Division, Immunoregulation, Medical Research Council National Institute for Medical Research, London, UK.
  • 2015  Associate Research Director (Group Leader Development), the Francis Crick Institute.