Imperial College London
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ProfessorDariusArmstrong-James

Faculty of Medicine, Department of Infectious Disease

Professor of Infectious Diseases and Medical Mycology
 
 
 
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Contact

 

d.armstrong

 
 
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Location

 

Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Amarsaikhan:2017:10.4049/jimmunol.1700078,
author = {Amarsaikhan, N and Sands, EM and Shah, A and Abdolrasouli, A and Reed, A and Slaven, JE and Armstrong-James, D and Templeton, SP},
doi = {10.4049/jimmunol.1700078},
journal = {Journal of Immunology},
pages = {624--632},
title = {Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis.},
url = {http://dx.doi.org/10.4049/jimmunol.1700078},
volume = {199},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA.
AU  - Amarsaikhan,N
AU  - Sands,EM
AU  - Shah,A
AU  - Abdolrasouli,A
AU  - Reed,A
AU  - Slaven,JE
AU  - Armstrong-James,D
AU  - Templeton,SP
DO  - 10.4049/jimmunol.1700078
EP  - 632
PY  - 2017///
SN  - 1550-6606
SP  - 624
TI  - Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis.
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.1700078
VL  - 199
ER  -
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