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

Academic Article

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.
  • Published In

  • Mucosal Immunology  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 11984787
  • Author List

  • Gopal R; Rangel-Moreno J; Slight S; Lin Y; Nawar HF; Fallert Junecko BA; Reinhart TA; Kolls J; Randall TD; Connell TD
  • Start Page

  • 972
  • End Page

  • 984
  • Volume

  • 6
  • Issue

  • 5