Fungal melanin suppresses airway epithelial chemokine secretion through blockade of calcium fluxing.
Nat Commun
; 15(1): 5817, 2024 Jul 10.
Article
in En
| MEDLINE
| ID: mdl-38987270
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aspergillus fumigatus
/
Calcium
/
Interleukin-8
/
Chemokine CXCL1
/
Melanins
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Commun
Year:
2024
Document type:
Article