Clofazimine enhances the efficacy of BCG revaccination via stem cell-like memory T cells

English version

Autoři: Shaheer Ahmad ^aff001; Debapriya Bhattacharya ^aff001; Neeta Gupta ^aff001; Varsha Rawat ^aff001; Sultan Tousif ^aff001; Luc Van Kaer ^aff002; Gobardhan Das ^aff001
Působiště autorů: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India ^aff001; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America ^aff002
Vyšlo v časopise: Clofazimine enhances the efficacy of BCG revaccination via stem cell-like memory T cells. PLoS Pathog 16(5): e1008356. doi:10.1371/journal.ppat.1008356
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008356

Souhrn

Tuberculosis (TB) is one of the deadliest diseases, claiming ~2 million deaths annually worldwide. The majority of people in TB endemic regions are vaccinated with Bacillus Calmette Guerin (BCG), which is the only usable vaccine available. BCG is efficacious against meningeal and disseminated TB in children, but protective responses are relatively short-lived and fail to protect against adult pulmonary TB. The longevity of vaccine efficacy critically depends on the magnitude of long-lasting central memory T (T_CM) cells, a major source of which is stem cell-like memory T (T_SM) cells. These T_SM cells exhibit enhanced self-renewal capacity as well as to rapidly respond to antigen and generate protective poly-functional T cells producing IFN-γ, TNF-α, IL-2 and IL-17. It is now evident that T helper Th 1 and Th17 cells are essential for host protection against TB. Recent reports have indicated that Th17 cells preserve the molecular signature for T_SM cells, which eventually differentiate into IFN-γ-producing effector cells. BCG is ineffective in inducing Th17 cell responses, which might explain its inadequate vaccine efficacy. Here, we show that revaccination with BCG along with clofazimine treatment promotes T_SM differentiation, which continuously restores T_CM and T effector memory (T_EM) cells and drastically increases vaccine efficacy in BCG-primed animals. Analyses of these T_SM cells revealed that they are predominantly precursors to host protective Th1 and Th17 cells. Taken together, these findings revealed that clofazimine treatment at the time of BCG revaccination provides superior host protection against TB by increasing long-lasting T_SM cells.

Klíčová slova:

Cytokines – Immune response – Long term memory – Memory T cells – Spleen – T cells – Tuberculosis – Vaccines

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