Taurine transport is a critical modulator of ionic fluxes during NLRP3 inflammasome activation

Peter Rossi-Smith¹, Joohee Kim¹, Kamil Skirlo², Trevor Ferris², Jack P Green³, Cari Stek⁴, Kristin K Huse⁵, Paige M Mortimer⁶, Antoni Olona¹, Cecilia Wieder⁷, Raymond Moseki⁴, Mariana Silva Dos Santos⁸, James I MacRae⁸, Shiranee Sriskandan⁵, Timothy M D Ebbels⁷, Robert J Wilkinson⁹, Alice E Denton⁶, Nicolas J Matheson¹⁰, Paras K Anand¹, Graeme Meintjes¹¹, David C Thomas¹², Rachel P J Lai¹³

Affiliations

¹ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK.
² Agilent Measurement Suite, Department of Chemistry, Imperial College London, London, UK.
³ Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, UK.
⁴ Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa.
⁵ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK; Centre for Bacterial Resistance Biology, Imperial College London, London, UK.
⁶ Department of Immunology and Inflammation, Imperial College London, London, UK.
⁷ Section of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
⁸ Metabolomics Science Technology Platform, Francis Crick Institute, London, UK.
⁹ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK; Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Tuberculosis Laboratory, Francis Crick Institute, London, UK.
¹⁰ Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK.
¹¹ Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Blizard Institute, Queen Mary University of London, London, UK.
¹² Department of Immunology and Inflammation, Imperial College London, London, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK.
¹³ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK. Electronic address: rachel.lai@imperial.ac.uk.

PMID: 40974575
DOI: 10.1016/j.celrep.2025.116317

Free article

Taurine transport is a critical modulator of ionic fluxes during NLRP3 inflammasome activation

Peter Rossi-Smith et al. Cell Rep. 2025.

Free article

. 2025 Sep 18;44(10):116317.

doi: 10.1016/j.celrep.2025.116317. Online ahead of print.

Authors

Affiliations

¹ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK.
² Agilent Measurement Suite, Department of Chemistry, Imperial College London, London, UK.
³ Division of Neuroscience, School of Biological Sciences, University of Manchester, Manchester, UK.
⁴ Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa.
⁵ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK; Centre for Bacterial Resistance Biology, Imperial College London, London, UK.
⁶ Department of Immunology and Inflammation, Imperial College London, London, UK.
⁷ Section of Bioinformatics, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
⁸ Metabolomics Science Technology Platform, Francis Crick Institute, London, UK.
⁹ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK; Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Tuberculosis Laboratory, Francis Crick Institute, London, UK.
¹⁰ Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK.
¹¹ Institute of Infectious Disease & Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Department of Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Blizard Institute, Queen Mary University of London, London, UK.
¹² Department of Immunology and Inflammation, Imperial College London, London, UK; Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK.
¹³ Section of Adult Infectious Disease, Department of Infectious Disease, Imperial College London, London, UK. Electronic address: rachel.lai@imperial.ac.uk.

PMID: 40974575
DOI: 10.1016/j.celrep.2025.116317

Abstract

Metabolic regulation is a key feature of inflammasome activation and effector function. Using metabolomic approaches, we show that downregulation of taurine metabolism is crucial for NLRP3 inflammasome activation. Following NLRP3 activation stimuli, taurine rapidly egresses to the extracellular compartment. Taurine efflux is facilitated primarily by the volume-regulated anion channel (VRAC). Loss of intracellular taurine impairs sodium-potassium ATPase pump activity, promoting ionic dysregulation and disrupting ionic fluxes. Inhibiting VRAC, or supplementation of taurine, restores the ionic balance, abrogates IL-1β release, and reduces cellular cytotoxicity in macrophages. We further demonstrate that the protective effect of taurine is diminished when sodium-potassium ATPase is inhibited, highlighting the pump's role in taurine-mediated protection. Finally, taurine metabolism is significantly associated with the development of tuberculosis-associated immune reconstitution inflammatory syndrome, a systemic hyperinflammatory condition known to be mediated by inflammasome activation. Altogether, we identified a critical metabolic pathway that modulates inflammasome activation and drives disease pathogenesis.

Keywords: ATPase; CP: Metabolism; inflammasome; inflammation; ion channels; ionic fluxes; metabolism; metabolomics; taurine; tuberculosis.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Taurine transport is a critical modulator of ionic fluxes during NLRP3 inflammasome activation

Affiliations

Taurine transport is a critical modulator of ionic fluxes during NLRP3 inflammasome activation

Authors

Affiliations

Abstract

Conflict of interest statement

LinkOut - more resources

Full Text Sources

Miscellaneous