Role of selenium and selenoproteins during mycobacterial infections

Abstract

Mycobacterium tuberculosis (M.tb) is responsible for Tuberculosis (TB), which is one of the deadliest infectious diseases and is the second leading cause of mortality due to a single infectious agent. Among the various risk factors of TB, undernutrition is a significant contributor. A deficiency in micronutrients facilitates the progression of TB infection to active TB. Selenium (Se) is one of the important micronutrients that facilitates immune function and redox homeostasis by incorporating into 25 known selenoproteins. These selenoproteins help regulate oxidative stress, support host bioenergetic health and may reduce the susceptibility to mycobacterial infections. However, their precise role in TB pathogenesis remains poorly understood. Our study investigates selenoprotein expression in TB infection and examines how selenium supplementation impacts the cell death pathways. Selenoprotein expression was analyzed in TB-infected and healthy individuals using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, in vitro studies on mycobacterial-infected cell cultures were performed to evaluate selenium’s impact on cell death pathways. We found that selenoprotein levels are dysregulated in TB-infected groups. Furthermore, our in vitro infection studies show that selenium supplementation promotes apoptosis during mycobacterial infection by enhancing the expression of pro-apoptotic proteins Bax and Bak, which are known to promote apoptotic cell death pathways. Thus, our study suggests that selenium and selenoproteins have the potential to play a crucial immunomodulatory function in TB infection.