Fungal melanin suppresses airway epithelial chemokine secretion through blockade of calcium fluxing.

Autor: Reedy JL; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Jensen KN; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Crossen AJ; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA., Basham KJ; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA., Ward RA; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA., Reardon CM; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA., Brown Harding H; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Hepworth OW; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Simaku P; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA., Kwaku GN; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA., Tone K; Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom.; Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan., Willment JA; Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom.; MRC Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom., Reid DM; Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom., Stappers MHT; Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom.; MRC Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom., Brown GD; Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom.; MRC Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom., Rajagopal J; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.; Harvard Stem Cell Institute, Cambridge, MA, USA.; Klarman Cell Observatory, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA., Vyas JM; Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. jvyas@mgh.harvard.edu.; Harvard Medical School, Boston, MA, USA. jvyas@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 10; Vol. 15 (1), pp. 5817. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1038/s41467-024-50100-x
Abstrakt: Respiratory infections caused by the human fungal pathogen Aspergillus fumigatus are a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been fully defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of the chemokines CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction in neutrophil recruitment to the apical airway both in vitro and in vivo. Aspergillus-derived melanin, a major constituent of the fungal cell wall, dampened airway epithelial chemokine secretion in response to fungi, bacteria, and exogenous cytokines. Furthermore, melanin muted pathogen-mediated calcium fluxing and hindered actin filamentation. Taken together, our results reveal a critical role for melanin interaction with airway epithelium in shaping the host response to fungal and bacterial pathogens.
(© 2024. The Author(s).)
Databáze: MEDLINE
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