[Application and prospects of human lung organoids and lung-on-a-chip in tuberculosis research]

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB) that poses a major threat to global public health. However, conventional cell models, animal models, and clinical samples cannot fully simulate human-specific immune responses to enable dynamic reconstruction of pathology. The unclear immune and pathogenic mechanisms have consistently been a bottleneck in the development of diagnostics, therapeutics, and preventive products for tuberculosis. As next-generation cell models, lung organoids and lung-on-a-chip systems represent a methodological innovation through three-dimensional bioengineering approaches. These approaches enable faster, simpler, and more accurate dynamic simulation of human lung physiology and the immune microenvironment. These models are already widely used in research on infectious respiratory diseases, chronic obstructive pulmonary disease, lung cancer, and other conditions, with preliminary applications also emerging in the field of tuberculosis. This article systematically summarizes the characteristics of lung organoids and lung-on-a-chip technologies and their research progress and application prospects in basic tuberculosis research, anti-tuberculosis drug development, tuberculosis vaccine evaluation, and tuberculosis comorbidity studies. These platforms offer innovative technological tools that could help to achieve the World Health Organization's strategic goal of ending tuberculosis, from exploring basic mechanisms to screening drugs and assessing clinical translation.