<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "Spatiotemporal regulation of ligand trafficking and TLR9 activation by PIEZO1 in human plasmacytoid dendritic cells"^^ . "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."^^ . "2026-01" . "9" . "resear" . . "American Association for the Advancement of Science (AAAS)"^^ . . . "Research (Wash. D.C.)"^^ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . "Nidhi"^^ . "Kalidas"^^ . "Nidhi Kalidas"^^ . . "Krishnananda"^^ . "Chattopadhyay"^^ . "Krishnananda Chattopadhyay"^^ . . "Tithi"^^ . "Mandal"^^ . "Tithi Mandal"^^ . . "Dipyaman"^^ . "Ganguly"^^ . "Dipyaman Ganguly"^^ . . "Upasana"^^ . "Mukhopadhyay"^^ . "Upasana Mukhopadhyay"^^ . . "Shrestha"^^ . "Pattanayak"^^ . "Shrestha Pattanayak"^^ . . "Deblina"^^ . "Raychaudhuri"^^ . "Deblina Raychaudhuri"^^ . . "Chinky Shiu Chen"^^ . "Liu"^^ . "Chinky Shiu Chen Liu"^^ . . "Fnu"^^ . "Ashish"^^ . "Fnu Ashish"^^ . . "Sumangal"^^ . "Roychowdhury"^^ . "Sumangal Roychowdhury"^^ . . "Bidisha"^^ . "Sinha"^^ . "Bidisha Sinha"^^ . . "Purbita"^^ . "Bandopadhyay"^^ . "Purbita Bandopadhyay"^^ . . . . . "HTML Summary of #3206 \n\nSpatiotemporal regulation of ligand trafficking and TLR9 activation by PIEZO1 in human plasmacytoid dendritic cells\n\n" . "text/html" . . . "QR Microbiology"@en . .