Modeling of lung-liver interaction during infection in a human fluidic organ-on-a-chip

Respiratory infections, including pneumonia and COVID-19, are major causes of global mortality and morbidity. Recent advancements in organ-on-a-chip (OOC) technologies have paved the way for human-based disease models, offering new tools for studying disease mechanisms and accelerating drug development. The aim of this study was to establish a lung-liver fluidic system to study the interaction of both organ modules during infection. A two organ (lung-liver) fluidic system was established using primary human bronchial (HBECs) or alveolar type epithelial cells (AT) for the lung module and Huh-7 cells for the liver module. Inactivated non-typeable Haemophilus influenzae (NTHi) and Pseudomonas aeruginosa PAO1 (PAO1) were applied to the lung module. Secreted mediators were screened by dot-blot analysis and quantified. The impact of bacteria-exposed epithelial cells on the liver cell transcriptome was analyzed via mRNA sequencing. Lung and liver cells established stable cultures in a circulatory fluidic system. Activation of HBECs or ATCs with NTHi or PAO1 resulted in the secretion of multiple inflammatory mediators into the microfluidic medium including tumor necrosis factor-alpha (TNF-

• Reinhold, S.
• Herr, C.
• Yao, Y.
• Pourrostami, M.
• Ritzmann, F.
• Lehr, T.
• Selzer, D.
• Kohl, Y.
• Yildiz, D.
• Slevogt, H.
• Beisswenger, C.
• Bals, R.