Curcumin Nanoparticles Enhance Mycobacterium bovis BCG Vaccine Efficacy by Modulating Host Immune Responses.

Shaheer Ahmad,Debapriya Bhattacharya,Gobardhan Das,Luc Van Kaer,Santosh Kar,Anand Ranganathan,Sabine Ehrt

doi:10.1128/iai.00291-19

Shaheer Ahmad, Debapriya Bhattacharya + Show 5 more

Open Access

https://doi.org/10.1128/iai.00291-19

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Abstract

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.

Highlights

Tuberculosis (TB) is one of the deadliest diseases, causing ϳ2 million deaths annually worldwide
We tested the capacity of nanocurcumin to modulate bacillus Calmette-Guérin (BCG) vaccine efficacy
Our observations demonstrated that nanocurcumin treatment in BCG-immunized mice significantly increased interferon gamma (IFN-␥)producing T helper 1 (Th1) and IL-17-producing Th17 cells, whereas the levels of IL-4-producing Th2 cells were moderately decreased (Fig. 7a)

Summary

Introduction

Tuberculosis (TB) is one of the deadliest diseases, causing ϳ2 million deaths annually worldwide. 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. One-third of the global population is infected with a latent form of TB, which represents an enormous reservoir waiting for an opportunity to reactivate disease [1]. Conditions such as HIV infection that impair immunity may lead to such TB reactivation [2]. One-third of the global population is latently infected with M. tuberculosis, the vast majority of individuals are resistant to TB, despite repeated exposure. Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only TB vaccine mainly effective against disseminated and meningeal TB in young children; it is likely that the November 2019 Volume 87 Issue 11 e00291-19

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