Protocol for Developing a Mouse Model of Post Primary Pulmonary Tuberculosis after Hematogenous Spread in Native Lungs and Lung Implants

Summary This protocol describes a mouse model of post-primary pulmonary tuberculosis (PTB) that develops after hematogenous spread from the primary lesion in native lungs and subcutaneous lung implants. It demonstrates that virulent Mycobacterium tuberculosis (Mtb) disseminates to lymphoid tissue in many organs, but selectively damages the lungs. This approach demonstrates a particular vulnerability of the lung tissue to virulent Mtb independent of the route of infection and provides a robust platform for examining lung-specific mechanisms driving TB pathology. Highlights Mouse model for studying mechanisms driving post-primary pulmonary TB progression in immune hosts Models a hematogenous spread of virulent Mycobacterium tuberculosis to the lungs from a primary site of infection Allows for the investigation of lung-specific mechanisms of TB susceptibility using lung tissue implants. Graphical abstract