Luteolin as a potential host-directed immunotherapy adjunct to isoniazid treatment of tuberculosis
Dhiraj Kumar Singh, Sultan Tousif, Ashima Bhaskar, Annu Devi, Kriti Negi, Barnani Moitra, Anand Ranganathan, Ved Prakash Dwivedi, Gobardhan Das
Abstract
Tuberculosis (TB) remains a major health problem throughout the world with one third of the population latently infected and ~1.74 million deaths annually. Current therapy consists of multiple antibiotics and a lengthy treatment regimen, which is associated with risk for the generation of drug-resistant Mycobacterium tuberculosis variants. Therefore, alternate host directed strategies that can shorten treatment length and enhance anti-TB immunity during the treatment phase are urgently needed. Here, we show that Luteolin, a plant-derived hepatoprotective immunomodulator, when administered along with isoniazid as potential host directed therapy promotes anti-TB immunity, reduces the length of TB treatment and prevents disease relapse. Luteolin also enhances long-term anti-TB immunity by promoting central memory T cell responses. Furthermore, we found that Luteolin enhances the activities of natural killer and natural killer T cells, both of which exhibit antitubercular attributes. Therefore, the addition of Luteolin to conventional antibiotic therapy may provide a means to avoid the development of drug-resistance and to improve disease outcome.