Early Secreted Antigen ESAT-6 of Mycobacterium tuberculosis Promotes Protective T Helper 17 Cell Responses in a Toll-Like Receptor-2-dependent Manner
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Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG) has been used as a tuberculosis (TB) vaccine since its development in 1921. BCG induces robust T helper 1 (Th1) immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb) infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6), expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1) exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1). However, TLR-2 knockout (TLR-2⁻/⁻) animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a) in dendritic cells (DCs), whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy.
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IL-17 is important to mount a protective T cell-mediated immune response against M. tuberculosis.
“On the other hand, IL-17 is important to mount a protective T cell-mediated immune response against M. tuberculosis (105)”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [105]
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- Authors
- Chatterjee, S., Dwivedi, V. P., Singh, Y., Siddiqui, I., Sharma, P., Van Kaer, L., Chattopadhyay, D., & Das, G.
- Affiliations
- International Centre for Genetic Engineering and Biotechnology (IN)
- International Centre for Genetic Engineering and Biotechnology (ZA)
- Indian Council of Medical Research (IN)
- Corresponding author
- Das, Gobardhan
- ORCID
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-11-10
- Volume
- 7
- Issue
- 11
- Pages
- e1002378
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC3213116
- OpenAlex
- W1968678975
- Cited by
- 153
- References
- 56
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 11 · 2021: 15 · 2020: 11 · 2019: 8 · 2018: 8 · 2017: 13 · 2016: 10 · 2015: 15 · 2014: 14 · 2013: 13 · 2012: 17
- FWCI
- 9.49
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust (WT01/GD/09/339)
- Department of Biotechnology, Ministry of Science and Technology, India
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- ESAT-6, Mycobacterium tuberculosis, Th17 cells, TLR2, MyD88 signaling, BCG vaccine, dendritic cells, interleukin-6, TGF-beta, microRNA-146a, tuberculosis vaccine efficacy, protective immunity, Mycobacterium tuberculosis H37Rv
- MeSH terms
- Animals, Antigens, Bacterial, Bacterial Proteins, BCG Vaccine, Dendritic Cells, Lung, Mice, Inbred C57BL, Mycobacterium bovis, Mycobacterium tuberculosis, Tuberculosis, Interleukin-6, Transforming Growth Factor beta, Mice, Knockout, Th1 Cells, Toll-Like Receptor 2, Mice, Myeloid Differentiation Factor 88, Th17 Cells
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