Interleukin-17-dependent CXCL13 mediates mucosal vaccine-induced immunity against tuberculosis

R. Gopal, J. Rangel-Moreno, S. Slight, Y. Lin, H. F. Nawar, B. A. Fallert Junecko, T. A. Reinhart, J. Kolls, T. D. Randall, T. D. Connell, S. A. Khader

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

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-γ (IFNγ)-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) T cells 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 IFNγ pathway as a new strategy to improve mucosal vaccines against TB.

Original languageEnglish
Pages (from-to)972-984
Number of pages13
JournalMucosal Immunology
Volume6
Issue number5
DOIs
StatePublished - Sep 2013

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