Recognition and control of neutrophil extracellular trap formation by MICL.

Autor: Malamud M; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Whitehead L; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK., McIntosh A; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK., Colella F; Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Aberdeen, UK., Roelofs AJ; Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Aberdeen, UK., Kusakabe T; Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; The Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, New York City, NY, USA., Dambuza IM; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK.; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK., Phillips-Brookes A; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Salazar F; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Perez F; Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada., Shoesmith R; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Zakrzewski P; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Sey EA; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Rodrigues C; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Morvay PL; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK.; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK., Redelinghuys P; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK., Bedekovic T; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Fernandes MJG; Faculty of Medicine, Department of Microbiology, Infectious Diseases, and Immunology, Laval University, Quebec City, Quebec, Canada., Almizraq R; Medical Affairs and Innovation, Canadian Blood Services, Toronto, Ontario, Canada., Branch DR; Medical Affairs and Innovation, Canadian Blood Services, Toronto, Ontario, Canada., Amulic B; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Harvey J; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK., Stewart D; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK., Yuecel R; Centre for Cytomics, University of Exeter, Exeter, UK., Reid DM; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK., McConnachie A; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK., Pickering MC; Department of Immunology and Inflammation, Imperial College London, London, UK., Botto M; Department of Immunology and Inflammation, Imperial College London, London, UK., Iliev ID; Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York City, NY, USA.; The Jill Roberts Institute for Research in Inflammatory Bowel Disease (JRI), Weill Cornell Medicine, New York City, NY, USA., McInnes IB; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK., De Bari C; Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Aberdeen, UK., Willment JA; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK.; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK., Brown GD; MRC Centre for Medical Mycology, University of Exeter, Exeter, UK. gordon.brown@exeter.ac.uk.; Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. gordon.brown@exeter.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Sep; Vol. 633 (8029), pp. 442-450. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1038/s41586-024-07820-3
Abstrakt: Regulation of neutrophil activation is critical for disease control. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA and neutrophil-derived proteins, are formed following pro-inflammatory signals; however, if this process is uncontrolled, NETs contribute to disease pathogenesis, exacerbating inflammation and host tissue damage 1,2 . Here we show that myeloid inhibitory C-type lectin-like (MICL), an inhibitory C-type lectin receptor, directly recognizes DNA in NETs; this interaction is vital to regulate neutrophil activation. Loss or inhibition of MICL functionality leads to uncontrolled NET formation through the ROS-PAD4 pathway and the development of an auto-inflammatory feedback loop. We show that in the context of rheumatoid arthritis, such dysregulation leads to exacerbated pathology in both mouse models and in human patients, where autoantibodies to MICL inhibit key functions of this receptor. Of note, we also detect similarly inhibitory anti-MICL autoantibodies in patients with other diseases linked to aberrant NET formation, including lupus and severe COVID-19. By contrast, dysregulation of NET release is protective during systemic infection with the fungal pathogen Aspergillus fumigatus. Together, we show that the recognition of NETs by MICL represents a fundamental autoregulatory pathway that controls neutrophil activity and NET formation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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