Curcumin, the bioactive component of turmeric also known as “Indian Yellow Gold,” exhibits therapeutic efficacy against several chronic inflammatory and infectious diseases. Even though considered as a wonder drug pertaining to a myriad of reported benefits, the translational potential of curcumin is limited by its low systemic bioavailability due to its poor intestinal absorption, rapid metabolism, and rapid systemic elimination. Therefore, the translational potential of this compound is specifically challenged by bioavailability issues, and several laboratories are making efforts to improve its bioavailability. We developed a simple one-step process to generate curcumin nanoparticles of ~200 nm in size, which yielded a fivefold enhanced bioavailability in mice over regular curcumin. Curcumin nanoparticles drastically reduced hepatotoxicity induced by antitubercular antibiotics during treatment in mice. Most interestingly, co-treatment of nanoparticle-formulated curcumin along with antitubercular antibiotics dramatically reduced the risk for disease reactivation and reinfection, which is the major shortfall of current antibiotic treatment adopted by Directly Observed Treatment Short-course. Furthermore, nanoparticle-formulated curcumin significantly reduced the time needed for antibiotic therapy to obtain sterile immunity, thereby reducing the possibility of generating drug-resistant variants of the organisms. Therefore, adjunct therapy of nano-formulated curcumin with enhanced bioavailability may be beneficial to treatment of tuberculosis and possibly other diseases.

Background: DOTS-treated patients exhibit vulnerability to reactivation and reinfection with TB, suggesting therapy-related immune impairment.Results: Isoniazid (INH) dramatically reduces Mycobacterium tuberculosis antigen-specific immune responses by inducing apoptosis in activated CD4+ T cells.Conclusion: Animals treated with INH exhibit post-treatment vulnerability to TB reinfection and reactivation.Significance: The immune-impairing effects of antibiotics need to be considered in TB treatment.

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.

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 shortlived 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 selfrenewal 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 BCGprimed 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.

The World Health Organization (WHO) estimates that the causative agent of tuberculosis (TB) currently infects one third of the global population and is responsible for about 2 million deaths among those infected annually. Current therapy for TB consists of multiple expensive antibiotics (Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol) and is lengthy, up to six months for drug-susceptible, and nine months or more for drug-resistant variants of TB. Although current TB treatment eradicates M.tb from the host body it also causes severe hepatotoxicity and other adverse side effects, causing a large number of patients to withdraw early from therapy. Additionally, displaying a phenomenon called therapy-related immune impairment; TB-treated patients are vulnerable to reactivation or reinfection of the disease. Once patients start feeling better, they often withdraw from treatment, especially those that live in resource-limited environments. Treatment withdrawal is largely responsible for the generation of drug-resistant variants of M.tb, including multidrug-resistant (MDR) and extremely drug-resistant (XDR) forms of M.tb. Therefore, new treatment approaches that reduce treatment regimen lengths and limit hepatotoxicity and other side effects are urgently needed.