| Autor: |
Reedy JL, Jensen KN, Crossen AJ, Basham KJ, Ward RA, Reardon CM, Harding HB, Hepworth OW, Simaku P, Kwaku GN, Tone K, Willment JA, Reid DM, Stappers MHT, Brown GD, Rajagopal J, Vyas JM |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 May 06. Date of Electronic Publication: 2024 May 06. |
| DOI: |
10.1101/2023.03.28.534632 |
| 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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