An Ex Vivo Lung Model of Mycobacterium tuberculosis (Mtb) Infectivity and the Early Host-Mtb Interaction

Digby Warner of the University of Cape Town in South Africa and Catherine Blish of Stanford University in the U.S. will explore human precision-cut lung slices (hPCLS) as an Mtb bioaerosol detection platform and model system for infection. Such a platform would provide an immediate read-out of Mtb infectivity and give insights into the initial Mtb-host interaction. They will determine the feasibility and reproducibility of using the hPCLS platform with samples containing extremely low numbers of Mtb bacilli, monitoring bacterial infectivity, replication, and dissemination by time-lapse fluorescence microscopy and examining key early events by cytometric and single-cell molecular assays. The platform could be used to answer specific questions, including whether Mtb organisms released during coughing by symptomatic TB patients are more infectious than those aerosolized during normal respiratory activities by asymptomatic individuals. It could also be applied at the site of aerosol sampling to guide and monitor preventative and therapeutic interventions.