Pattanayak, Shrestha and Raychaudhuri, Deblina and Bandopadhyay, Purbita and Mukhopadhyay, Upasana and Mandal, Tithi and Liu, Chinky Shiu Chen and Kalidas, Nidhi and Roychowdhury, Sumangal and Chattopadhyay, Krishnananda and Ashish, Fnu and Sinha, Bidisha and Ganguly, Dipyaman (2026) Spatiotemporal regulation of ligand trafficking and TLR9 activation by PIEZO1 in human plasmacytoid dendritic cells. Research (Wash. D.C.), 9 (resear). p. 1067.
Full text not available from this repository. (Request a copy)Abstract
Plasmacytoid dendritic cells (pDCs) are innate immune cells that produce type I interferons (IFNs) upon sensing nucleic acids via Toll-like receptor 9 (TLR9). Synthetic oligodeoxynucleotides CpGA and CpGB are widely used TLR9 agonists, yet only CpGA robustly induces IFN-α in pDCs. In contrast, CpGB drives much less IFN production. The mechanism underlying this ligand-specific response is not known. Here, we identify PIEZO1, a mechanosensory ion channel, as a regulator for this ligand-specific response. We show that CpGA, unlike CpGB, self-associates into large aggregates that generate membrane tension during cellular uptake, activating PIEZO1. This triggers calcium influx and localized F-actin assembly, retaining CpGA in early endosomes to sustain IRF7 activation and IFN production. PIEZO1 deficiency or inhibition abolishes CpGA-induced IFN responses, while PIEZO1 activation enhances IFN production by CpGB. Our findings reveal a hitherto unknown biophysical checkpoint in TLR9 signaling, where PIEZO1 translates membrane tension into spatially controlled TLR9 signaling. This study uncovers a novel role for mechanosensing in nucleic acid immunity, with implications for modulating IFN responses in infections and autoimmunity.
| Item Type: | Article |
|---|---|
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 01 Feb 2026 03:24 |
| Last Modified: | 01 Feb 2026 03:24 |
| URI: | http://crdd.osdd.net/open/id/eprint/3206 |
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