Experimental study of tuberculosis: From animal models to complex cell systems and organoids

Tuberculosis (TB) is a devastating disease to mankind that has killed more people than any other infectious disease.Despite many efforts and successes from the scientific and health communities, the prospect of TB elimination remains distant.On the one hand, sustainable public health programs with affordable and broad implementation of anti-TB measures are needed.On the other hand, achieving TB elimination requires critical advances in three areas: vaccination, diagnosis, and treatment.It is also well accepted that succeeding in advancing these areas requires a deeper knowledge of host-pathogen interactions during infection, and for that, better experimental models are needed.Here, we review the potential and limitations of different experimental approaches used in TB research, focusing on animal and human-based cell culture models.We highlight the most recent advances in developing in vitro 3D models and introduce the potential of lung organoids as a new tool to study Mycobacterium tuberculosis infection. Author summaryTuberculosis (TB) is the number 1 killer in the world due to a bacterial infection.The study of this disease through clinical and epidemiological data and through the use of different experimental models has provided important knowledge on the role of the immune response generated during infection.This is critical for the development of novel vaccines and therapeutic strategies.However, in spite of the advances made, it is well accepted that better models are needed to study TB.This review discusses the different models used to study TB, highlighting the advantages and disadvantages of the available animal and cellular models and introducing recently developed state-of-the-art approaches based on human-based cell culture systems.These new advances are integrated in a road map for future study of TB, converging for the potential of lung organoids in TB research.