• Open Access

Enhanced protection to Mycobacterium tuberculosis infection in IL-10-deficient mice is accompanied by early and enhanced Th1 responses in the lung

Authors

  • Paul S. Redford,

    1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
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  • Andre Boonstra,

    1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
    2. Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Simon Read,

    1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
    2. Biopharmaceuticals Research Unit, Maløv, Denmark
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  • Jonathan Pitt,

    1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
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  • Christine Graham,

    1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
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  • Evangelos Stavropoulos,

    1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
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  • Gregory J. Bancroft,

    1. Immunology Unit, Department of Infectious & Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
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  • Anne O'Garra

    Corresponding author
    1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
    • Division of Immunoregulation, MRC NIMR, The Ridgeway, Mill Hill, London, NW7 1AA, UK Fax: +44-208-816-2564
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Abstract

IL-10 regulates the balance of an immune response between pathogen clearance and immunopathology. We show here that Mycobacterium tuberculosis (Mtb) infection in the absence of IL-10 (IL-10−/− mice) results in reduced bacterial loads in the lung. This reduction was preceded by an accelerated and enhanced IFN-γ response in the lung, an increased influx of CD4+ T cells into the lung, and enhanced production of chemokines and cytokines, including CXCL10 and IL-17, in both the lung and the serum. Neutralization of IL-17 affected neither the enhanced production of CXCL10 nor the accumulation of IFN-γ-producing T cells in the lungs, but led to reduced numbers of granulocytes in the lung and reduced bacterial loads in the spleens of Mtb-infected mice. This suggests that IL-17 may contribute to dissemination of Mtb.

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