IL‐23‐dependent IL‐17 drives Th1‐cell responses following Mycobacterium bovis BCG vaccination
Open Access
- 21 November 2011
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 42 (2), 364-373
- https://doi.org/10.1002/eji.201141569
Abstract
The generation of effective type 1 T helper (Th1)‐cell responses is required for immunity against intracellular bacteria. However, some intracellular bacteria require interleukin (IL)‐17 to drive Th1‐cell immunity and subsequent protective host immunity. Here, in a model of Mycobacterium bovis Bacille Calmette–Guerin (BCG) vaccination in mice, we demonstrate that the dependence on IL‐17 to drive Th1‐cell responses is a host mechanism to overcome bacteria‐induced IL‐10 inhibitory effects. We show that BCG‐induced prostaglandin‐E2 (PGE2) promotes the production of IL‐10 which limits Th1‐cell responses, while simultaneously inducing IL‐23 and Th17‐cell differentiation. The ability of IL‐17 to downregulate IL‐10 and induce IL‐12 production allows the generation of subsequent Th1‐cell responses. Accordingly, BCG‐induced Th17‐cell responses precede the generation of Th1‐cell responses in vivo, whereas the absence of the IL‐23 pathway decreases BCG vaccine‐induced Th17 and Th1‐cell immunity and subsequent vaccine‐induced protection upon M. tuberculosis challenge. Importantly, in the absence of IL‐10, BCG‐induced Th1‐cell responses occur in an IL‐17‐independent manner. These novel data demonstrate a role for the IL‐23/IL‐17 pathway in driving Th1‐cell responses, specifically to overcome IL‐10‐mediated inhibition and, furthermore, show that in the absence of IL‐10, the generation of BCG‐induced Th1‐cell immunity is IL‐17 independent.Keywords
This publication has 38 references indexed in Scilit:
- Enhanced protection to Mycobacterium tuberculosis infection in IL‐10‐deficient mice is accompanied by early and enhanced Th1 responses in the lungEuropean Journal of Immunology, 2010
- Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensisImmunity, 2009
- Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signalingThe Journal of Experimental Medicine, 2009
- The Biological Functions of T Helper 17 Cell Effector Cytokines in InflammationImmunity, 2008
- Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapyCytokine, 2008
- A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17Nature Immunology, 2005
- Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineagesNature Immunology, 2005
- IL-23 drives a pathogenic T cell population that induces autoimmune inflammationThe Journal of Experimental Medicine, 2005
- Rapid Induction of Tumor-specific Type 1 T Helper Cells in Metastatic Melanoma Patients by Vaccination with Mature, Cryopreserved, Peptide-loaded Monocyte-derived Dendritic CellsThe Journal of Experimental Medicine, 2002
- Erasing the World's Slow Stain: Strategies to Beat Multidrug-Resistant TuberculosisScience, 2002