Fungal melanin suppresses airway epithelial chemokine secretion through blockade of calcium fluxing.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 Jul 2024
10 Jul 2024
Historique:
received:
02
04
2023
accepted:
28
06
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
10
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38987270
doi: 10.1038/s41467-024-50100-x
pii: 10.1038/s41467-024-50100-x
doi:
Substances chimiques
Melanins
0
Interleukin-8
0
Calcium
SY7Q814VUP
Chemokine CXCL1
0
CXCL8 protein, human
0
CXCL1 protein, human
0
Chemokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5817Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01AI136529
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : K08AI14755
Organisme : U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health)
ID : R01AI150181
Organisme : Wellcome Trust
ID : 102705
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 217163
Pays : United Kingdom
Informations de copyright
© 2024. The Author(s).
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