A lung-on-chip model reveals an essential role for alveolar epithelial cells in controlling bacterial growth during early tuberculosis

• DOI: 10.1101/2020.02.03.931170
• Publication Date: 2020-02-04T05:45:13Z
• Authors: Vivek V. Thacker; Neeraj Dhar; Kunal Sharma; Riccardo Barrile; Katia Karalis; John D. McKinney
• Keywords: Intracellular parasite

Abstract Mycobacterium tuberculosis (Mtb) makes ‘first contact’ with a host in the alveolar space, an interaction largely inaccessible to experimental observation. We establish lung-on-chip model for early and use time-lapse imaging reveal dynamics of host-Mtb interactions at air-liquid interface spatiotemporal resolution unattainable animal models. By reconstituting physiology modular manner, we probe role pulmonary surfactant secreted by epithelial cells (AECs) infection. This is difficult study directly models, as surfactant-deficient animals are either non-viable or develop acute lung pathologies. demonstrate that deficiency results rapid uncontrolled Mtb growth both macrophages AECs. In contrast, under normal levels, significant fraction intracellular bacteria non-growing. The phenotype rescued exogenous addition replacement formulations, which have no effect on bacterial viability absence cells. Surfactant partially removes virulence-associated lipids proteins 1,2 from cell surface consistent this mechanism action, show attenuation lacking ESX-1 secretion system independent levels. These findings may partly explain why individuals compromised function, such smokers elderly persons, increased risk developing active tuberculosis.