Interleukin-17-dependent CXCL-13 mediates mucosal vaccine-induced immunity against tuberculosis

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 17 (Th17) responses and provide vaccine-induced protection against Mtb infection. Importantly, protection is Interferon-γ(IFNγ)-independent but Interleukin (IL-17)-dependent. Our data show that IL-17 mediates CXCL13 induction in the lung for strategic localization of pro-inflammatory cytokine-producing CXCR5(+) 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.