Targeting dendritic cells with TLR-2 ligand-coated nanoparticles loaded with Mycobacterium tuberculosis epitope induce antituberculosis immunity
DIR@IMTECH: CSIR-Institute of Microbial Technology
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Title |
Targeting dendritic cells with TLR-2 ligand-coated nanoparticles loaded with Mycobacterium tuberculosis epitope induce antituberculosis immunity
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Creator |
Das, Deepjyoti Kumar
Zafar, Mohammad Adeel Nanda, Sidhanta Singh, Sanpreet Lamba, Taruna Bashir, Hilal Singh, Pargat Maurya, Sudeep Kumar Nadeem, Sajid Sehrawat, Sharvan Bhalla, Vijayender Agrewala, Javed Naim |
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Subject |
QR Microbiology
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Description |
ovel vaccination strategies are crucial to efficiently control tuberculosis, as proposed by the World Health Organization under its flagship program “End TB Strategy.” However, the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), particularly in those coinfected with HIV-AIDS, constitutes a major impediment to achieving this goal. We report here a novel vaccination strategy that involves synthesizing a formulation of an immunodominant peptide derived from the Acr1 protein of Mtb. This nanoformulation in addition displayed on the surface a toll-like receptor-2 ligand to offer to target dendritic cells (DCs). Our results showed an efficient uptake of such a concoction by DCs in a predominantly toll-like receptor-2–dependent pathway. These DCs produced elevated levels of nitric oxide, proinflammatory cytokines interleukin-6, interleukin-12, and tumor necrosis factor-α, and upregulated the surface expression of major histocompatibility complex class II molecules as well as costimulatory molecules such as CD80 and CD86. Animals injected with such a vaccine mounted a significantly higher response of effector and memory Th1 cells and Th17 cells. Furthermore, we noticed a reduction in the bacterial load in the lungs of animals challenged with aerosolized live Mtb. Therefore, our findings indicated that the described vaccine triggered protective anti-Mtb immunity to control the tuberculosis infection.
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Publisher |
Elsevier
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Date |
2022-12
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Type |
Article
PeerReviewed |
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Relation |
https://www.jbc.org/article/S0021-9258(22)01039-0/fulltext
http://crdd.osdd.net/open/3072/ |
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Identifier |
Das, Deepjyoti Kumar and Zafar, Mohammad Adeel and Nanda, Sidhanta and Singh, Sanpreet and Lamba, Taruna and Bashir, Hilal and Singh, Pargat and Maurya, Sudeep Kumar and Nadeem, Sajid and Sehrawat, Sharvan and Bhalla, Vijayender and Agrewala, Javed Naim (2022) Targeting dendritic cells with TLR-2 ligand-coated nanoparticles loaded with Mycobacterium tuberculosis epitope induce antituberculosis immunity. JOURNAL OF BIOLOGICAL CHEMISTRY, 298 (12).
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