TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection

Jing Geng, Yiran Shi, Jinjia Zhang, Bingying Yang, Ping Wang, Weihong Yuan, Hao Zhao, Junhong Li, Funiu Qin, Lixin Hong, Changchuan Xie, Xianming Deng, Yujie Sun, Congying Wu, Lanfen Chen () and Dawang Zhou ()
Additional contact information
Jing Geng: Xiamen University
Yiran Shi: Xiamen University
Jinjia Zhang: Xiamen University
Bingying Yang: Xiamen University
Ping Wang: Xiamen University
Weihong Yuan: The Second Affiliated Hospital of Xi’an Jiaotong University
Hao Zhao: Xiamen University
Junhong Li: Xiamen University
Funiu Qin: Xiamen University
Lixin Hong: Xiamen University
Changchuan Xie: Xiamen University
Xianming Deng: Xiamen University
Yujie Sun: Peking University
Congying Wu: Peking University Health Science Center
Lanfen Chen: Xiamen University
Dawang Zhou: Xiamen University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23683-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23683-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23683-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().