Abstract
Background Tuberculosis (TB) remains a major global public health problem and the leading cause of mortality by a single infectious agent. TB is a chronic infectious disease that is primarily caused by Mycobacterium tuberculosis (Mtb). Macrophage (Mφ) are the main hosts of Mtb, the interaction between Mtb and Mφ plays an important role in the pathogenesis of TB.Summary The macrophages used in the current study are mostly derived from tumor cell lines or peripheral blood mononuclear cells (PBMC), but the application of such cells still have many problems needed to be sloved, such as the loss of function due to changes in genetic structure and the difficulty in cell acquisition. Human induced pluripotent stem cells (hiPS) represent an innovative source for the standardized in vitro generation of Mφ, and show novel promise in exploring disease pathogenesis, particularly TB. Current studies have revealed that autophagy plays a central role in the interaction between Mtb and Mφ, but the molecular mechanism involoved remains unclear and the exact role of hiPS-derived macrophages (hiPS-Mφ) in regulating autophagy induced by Mtb also remains unclear. To investigate the similarities and differences in hiPS-Mφ and THP-1-Mφ in anti-tuberculosis immunity, this study successfully obtained macrophages derived from hiPS and THP-1, then explored the mechanism behind Bacillus Calmette-Guerin (BCG)-induced autophagy through transcriptome sequencing analysis, qPCR, Western Blot Analysis and cell submicroscopic structure observation etc.. Our findings revealed that BCG infection of hiPS-Mφ and THP-1-Mφ would promote autophagy by regulating the expression of autophagy-related genes, which also indicated that the BCG-induced autophagy in hiPS-Mφ and THP-1-Mφ may be associated with PI3K/AKT/mTOR signaling pathway. However, there are some differences in the mechanism by which BCG infects macrophages from different sources and induces autophagy. Considering the above findings, we have provided novel insights into the role of macrophages along with autophagy in the anti-tuberculosis immune mechanism and the possibility of establishing an in vitro hiPS-Mφ-TB disease model.
Advanced In Vitro Lung Models for Drug and Toxicity Screening: The Promising Role of Induced Pluripotent Stem Cells
