TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection
| Autor: | Jinjia Zhang, Yiran Shi, Jing Geng, Weihong Yuan, Ping Wang, Hao Zhao, Dawang Zhou, Bingying Yang, Xianming Deng, Funiu Qin, Lixin Hong, Yujie Sun, Junhong Li, Lanfen Chen, Congying Wu, Changchuan Xie |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
rac1 GTP-Binding Protein 0301 basic medicine General Physics and Astronomy Stimulation Serine-Threonine Kinase 3 Ion Channels Mice 0302 clinical medicine Phagosomes Fluorescence Resonance Energy Transfer Macrophage Cytoskeleton Escherichia coli Infections Innate immunity Multidisciplinary Hepatocyte Growth Factor Bacterial Infections Bacterial host response Cell biology Infection Signal Transduction Science Phagocytosis RAC1 Protein Serine-Threonine Kinases Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immunity Proto-Oncogene Proteins Ca2+/calmodulin-dependent protein kinase Animals Humans Innate immune system Macrophages Neuropeptides General Chemistry Actins Immunity Innate Toll-like receptors Mice Inbred C57BL Toll-Like Receptor 4 HEK293 Cells 030104 developmental biology TLR4 Calcium Calcium-Calmodulin-Dependent Protein Kinase Type 2 Reactive Oxygen Species 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | TLR4 signaling plays key roles in the innate immune response to microbial infection. Innate immune cells encounter different mechanical cues in both health and disease to adapt their behaviors. However, the impact of mechanical sensing signals on TLR4 signal-mediated innate immune response remains unclear. Here we show that TLR4 signalling augments macrophage bactericidal activity through the mechanical sensor Piezo1. Bacterial infection or LPS stimulation triggers assembly of the complex of Piezo1 and TLR4 to remodel F-actin organization and augment phagocytosis, mitochondrion-phagosomal ROS production and bacterial clearance and genetic deficiency of Piezo1 results in abrogation of these responses. Mechanistically, LPS stimulates TLR4 to induce Piezo1-mediated calcium influx and consequently activates CaMKII-Mst1/2-Rac axis for pathogen ingestion and killing. Inhibition of CaMKII or knockout of either Mst1/2 or Rac1 results in reduced macrophage bactericidal activity, phenocopying the Piezo1 deficiency. Thus, we conclude that TLR4 drives the innate immune response via Piezo1 providing critical insight for understanding macrophage mechanophysiology and the host response. Innate immune cells respond to a number of environmental cues including TLR signalling. Here the authors implicate mechanical sensor Piezo1 in the TLR4 mediated host response to bacterial infection and implicate it in the enhancement of macrophage mediated host response. |
| Databáze: | OpenAIRE |
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