Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity

• Published in: Nature (London) Vol. 573; no. 7772; pp. 69 - 74
• Main Authors: Solis, Angel G., Bielecki, Piotr, Steach, Holly R., Sharma, Lokesh, Harman, Christian C. D., Yun, Sanguk, de Zoete, Marcel R., Warnock, James N., To, S. D. Filip, York, Autumn G., Mack, Matthias, Schwartz, Martin A., Dela Cruz, Charles. S., Palm, Noah W., Jackson, Ruaidhrí, Flavell, Richard A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2019; Nature Publishing Group
• Subjects: 13/21; 13/31; 14/1; 14/63; 38/39; 38/90; 38/91; 42/109; 42/41; 42/44; 631/250/262; 631/250/516; Ablation; Animals; Bacterial diseases; Bacterial infections; Endothelin-1 - metabolism; Female; Fibrosis; Gene expression; Humanities and Social Sciences; Hydrostatic Pressure; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immune response; Immune system; Immunity; Immunity, Innate; Infections; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - microbiology; Inflammatory response; Innate immunity; Ion channels; Ion Channels - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; Life cycles; Lung - immunology; Lung - metabolism; Lung - microbiology; Lungs; Macrophages - immunology; Macrophages - metabolism; Male; Mechanical properties; Mechanotransduction; Mechanotransduction, Cellular - immunology; Mice; Motility; multidisciplinary; Nutrient availability; Oxygen; Physiological aspects; Physiology; Pressure; Pseudomonas aeruginosa - immunology; Pseudomonas Infections - immunology; Pulmonary arteries; Pulmonary fibrosis; Science; Science (multidisciplinary); Signal Transduction; Variation; United States
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-019-1485-8

Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity. PIEZO1 signalling mediates activation of a proinflammatory response to cyclical pressure fluctuations in immune cells.