Journal
MICROBES AND INFECTION
Volume 13, Issue 12-13, Pages 1099-1110Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2011.06.012
Keywords
IL-24; Mycobacterium tuberculosis; Cytokine immunotherapy
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Funding
- National Grand Program on Key Infectious Disease [2008ZX10003-005]
- National Natural Science Foundation of China [30921001, 30800038]
- National Outstanding Youth Foundation of China [81025008]
- 973 Program of China [2009CB522507]
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Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a major global health problem. Interleukin 24 (IL-24) is a novel tumor suppressor and a unique member of the IL-10 family of cytokines. However, the in vivo immunological consequences of this cytokine's activity during Mtb infection are still unknown. We found that IL-24 concentration was significantly decreased in the sera of TB patients, and Mtb infection suppressed IL-24 expression of human peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, we used a mouse infection model utilizing the virulent Mtb H37Rv strain to demonstrate that the administration of exogenous IL-24 had a protective effect against the bacteria. We found that IL-24 could activate human CD8(+) T cells, driving CD8(+) T cells to produce interferon-gamma (IFN-gamma) and counteract TB. This activity was found to be dependent on early involvement of neutrophils in the mouse model. IL-24 strongly stimulated IFN-gamma production mainly by signaling through the IL-24 receptors of human CD8(+) T cells. IL-12 secretion from neutrophils in response to IL-24 treatment might be a minor factor in activating human CD8(+) T cells to secrete IFN-gamma. Suppression of IL-24 expression by Mtb infection might enhance susceptibility to infection and promote the development of chronic TB. This new information could potentially stimulate the development of a new cytokine-based immunotherapeutic approach using IL-24 to stimulate immunity against TB. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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