Journal
MUCOSAL IMMUNOLOGY
Volume 6, Issue 5, Pages 972-984Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2012.135
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Funding
- Children's Hospital of Pittsburgh
- NIH [AI083541, HL105427, HL69409, DE13833, AI060422]
- Department of Medicine, University of Rochester
- Research Advisory Committee Grants from Children's Hospital of Pittsburgh of the UPMC Health System
- [AI91036]
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The variable efficacy of tuberculosis (TB) vaccines and the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) emphasize the urgency for not only generating new and more effective vaccines against TB but also understanding the underlying mechanisms that mediate vaccine-induced protection. We demonstrate that mucosal adjuvants, such as type II heat labile enterotoxin (LT-IIb), delivered through the mucosal route induce pulmonary Mtb-specific T helper type 17 (Th17) responses and provide vaccine-induced protection against Mtb infection. Importantly, protection is interferon-gamma (IFN gamma)-independent but interleukin-17 (IL-17)-dependent. Our data show that IL-17 mediates C-X-C motif chemokine ligand 13 (CXCL13) induction in the lung for strategic localization of proinflammatory cytokine-producing CXCR5(+) (C-X-C motif chemokine receptor 5-positive) Tcells within lymphoid structures, thereby promoting early and efficient macrophage activation and the control of Mtb. Our studies highlight the potential value of targeting the IL-17-CXCL13 pathway rather than the IFN gamma pathway as a new strategy to improve mucosal vaccines against TB.
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