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Open AccessArticle

Antigen-Specific IFN-γ/IL-17-Co-Producing CD4+ T-Cells are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine

1
Department of Microbiology, and Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea
2
Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Vaccines 2020, 8(2), 300; https://doi.org/10.3390/vaccines8020300
Received: 7 May 2020 / Revised: 23 May 2020 / Accepted: 9 June 2020 / Published: 11 June 2020
The antigen-specific Th17 responses in the lungs for improved immunity against Mycobacterium tuberculosis (Mtb) infection are incompletely understood. Tuberculosis (TB) vaccine candidate HSP90-ESAT-6 (E6), given as a Bacillus Calmette-Guérin (BCG)-prime boost regimen, confers superior long-term protection against the hypervirulent Mtb HN878 infection, compared to BCG or BCG-E6. Taking advantage of protective efficacy lead-out, we found that ESAT-6-specific multifunctional CD4+IFN-γ+IL-17+ T-cells optimally correlated with protection level against Mtb infection both pre-and post-challenge. Macrophages treated with the supernatant of re-stimulated lung cells from HSP90-E6-immunised mice significantly restricted Mtb growth, and this phenomenon was abrogated by neutralising anti-IFN-γ and/or anti-IL-17 antibodies. We identified a previously unrecognised role for IFN-γ/IL-17 synergism in linking anti-mycobacterial phagosomal activity to enhance host control against Mtb infection. The implications of our findings highlight the fundamental rationale for why and how Th17 responses are essential in the control of Mtb, and for the development of novel anti-TB subunit vaccines. View Full-Text
Keywords: Mycobacterium tuberculosis; BCG-prime boost; IFN-γ/IL-17; multifunctional T cells; phagosome maturation Mycobacterium tuberculosis; BCG-prime boost; IFN-γ/IL-17; multifunctional T cells; phagosome maturation
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Choi, H.-G.; Kwon, K.W.; Choi, S.; Back, Y.W.; Park, H.-S.; Kang, S.M.; Choi, E.; Shin, S.J.; Kim, H.-J. Antigen-Specific IFN-γ/IL-17-Co-Producing CD4+ T-Cells are the Determinants for Protective Efficacy of Tuberculosis Subunit Vaccine. Vaccines 2020, 8, 300.

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