TY - JOUR
T1 - Curcumin nanoparticles enhance mycobacterium bovis BCG vaccine efficacy by modulating host immune responses
AU - Ahmad, Shaheer
AU - Bhattacharya, Debapriya
AU - Kar, Santosh
AU - Ranganathan, Anand
AU - Van Kaer, Luc
AU - Das, Gobardhan
N1 - Funding Information:
This work was supported by the Department of Biotechnology, Government of India (grant BT/PR6312/MED/29/605/2012), DST Purse Phase-II, SCMM (core research grant), and the Council of Scientific and Industrial Research (CSIR), which provided a Junior Research Fellowship and a Senior Research Fellowship to Shaheer Ahmad and a Senior Research Associateship to Debapriya Bhattacharya (pool scientist scheme; pool no. 8802/A).
Funding Information:
We acknowledge the support of the Department of Biotechnology-supported Tuberculosis Aerosol Challenge Facility at the ICGEB and their staff in accomplishing this work. We thank the SCMM (JNU) and the ICGEB, New Delhi, where the work was accomplished. We also thank Sultan Tausif and Samit Chattarjee for their kind support. This work was supported by the Department of Biotechnology, Government of India (grant BT/PR6312/MED/29/605/2012), DST Purse Phase-II, SCMM (core research grant), and the Council of Scientific and Industrial Research (CSIR), which provided a Junior Research Fellowship and a Senior Research Fellowship to Shaheer Ahmad and a Senior Research Associateship to Debapriya Bhattacharya (pool scientist scheme; pool no. 8802/A). S.A. and D.B. designed the experiments, did the work, analyzed it, and wrote the paper. S.K. prepared nanocurcumin and determined its bioavailability and size. Moreover, he also helped in writing the manuscript. A.R. and L.V.K. helped in editing the paper. G.D. designed and supervised the experiments, analyzed the data, and wrote the paper. All authors have submitted the ICMJE form for disclosure of potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Publisher Copyright:
Copyright © 2019 Ahmad et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2019
Y1 - 2019
N2 - Tuberculosis (TB) is one of the deadliest diseases, causing ~2 million deaths annually worldwide. Mycobacterium bovis bacillus Calmette-Guérin (BCG), the only TB vaccine in common use, is effective against disseminated and meningeal TB in young children but is not effective against adult pulmonary TB. T helper 1 (Th1) cells producing interferon gamma (IFN-γ) and Th17 cells producing interleukin-17 (IL-17) play key roles in host protection against TB, whereas Th2 cells producing IL-4 and regulatory T cells (Tregs) facilitate TB disease progression by inhibiting protective Th1 and Th17 responses. Furthermore, the longevity of vaccine efficacy critically depends on the magnitude of long-lasting central memory T (TCM) cell responses. Hence, immunomodulators that promote TCM responses of the Th1 and Th17 cell lineages may improve BCG vaccine efficacy. Here, we show that curcumin nanoparticles enhance various antigen-presenting cell (APC) functions, including autophagy, costimulatory activity, and the production of inflammatory cytokines and other mediators. We further show that curcumin nanoparticles enhance the capacity of BCG to induce TCM cells of the Th1 and Th17 lineages, which augments host protection against TB infection. Thus, curcumin nanoparticles hold promise for enhancing the efficacy of TB vaccines.
AB - Tuberculosis (TB) is one of the deadliest diseases, causing ~2 million deaths annually worldwide. Mycobacterium bovis bacillus Calmette-Guérin (BCG), the only TB vaccine in common use, is effective against disseminated and meningeal TB in young children but is not effective against adult pulmonary TB. T helper 1 (Th1) cells producing interferon gamma (IFN-γ) and Th17 cells producing interleukin-17 (IL-17) play key roles in host protection against TB, whereas Th2 cells producing IL-4 and regulatory T cells (Tregs) facilitate TB disease progression by inhibiting protective Th1 and Th17 responses. Furthermore, the longevity of vaccine efficacy critically depends on the magnitude of long-lasting central memory T (TCM) cell responses. Hence, immunomodulators that promote TCM responses of the Th1 and Th17 cell lineages may improve BCG vaccine efficacy. Here, we show that curcumin nanoparticles enhance various antigen-presenting cell (APC) functions, including autophagy, costimulatory activity, and the production of inflammatory cytokines and other mediators. We further show that curcumin nanoparticles enhance the capacity of BCG to induce TCM cells of the Th1 and Th17 lineages, which augments host protection against TB infection. Thus, curcumin nanoparticles hold promise for enhancing the efficacy of TB vaccines.
KW - APCs
KW - BCG vaccine
KW - Curcumin nanoparticles
KW - K1.3 potassium ion channel
KW - Memory T cells
KW - Mycobacterium tuberculosis
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U2 - 10.1128/IAI.00291-19
DO - 10.1128/IAI.00291-19
M3 - Article
C2 - 31481412
AN - SCOPUS:85073577989
VL - 87
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 11
M1 - e00291-19
ER -