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Measuring Phagocytosis of Aspergillus fumigatus Conidia by Human Leukocytes using Flow Cytometry
Published on: December 7, 2019
Human Bronchial Epithelial Cells Inhibit Aspergillus fumigatus Germination of Extracellular Conidia via FleA
Nicolas Richard1, Léa Marti1, Annabelle Varrot2
1Sorbonne Université, UPMC Univ. Paris 06, Inserm, Centre de Recherche Saint-Antoine Paris, Paris, France.
Abstract:
Aspergillus fumigatus is an environmental filamentous fungus that may act as an opportunistic pathogen causing a variety of diseases, including asthma or allergic bronchopulmonary aspergillosis, and infection, ranging from asymptomatic colonization to invasive pulmonary form, especially in immunocompromised patients. This fungus is characterized by different morphotypes including conidia which are the infective propagules able to germinate into hyphae. Due to their small size (2-3 µm), conidia released in the air can reach the lower respiratory tract. The objective of this study was to characterize the interactions between conidia and bronchial epithelial cells. To this end, we studied the role of bronchial epithelial cells, i.e., the BEAS-2B cell line and human primary cells, in conidial germination of a laboratory strain and three clinical strains of A. fumigatus. Microscopic observations and galactomannan measurements demonstrated that contact between epithelial cells and conidia leads to the inhibition of conidia germination. We demonstrated that this fungistatic process is not associated with the release of any soluble components nor internalization by the epithelial cells. We highlight that this antifungal process involves the phosphoinositide 3-kinase pathway on the host cellular side and the lectin FleA on the fungal side. Collectively, our results show that bronchial epithelial cells attenuate fungal virulence by inhibiting germination of extracellular conidia, thus preventing the morphological change from conidia to filaments, which is responsible for tissue invasion.
Insights
Bronchial epithelial cells prevent Aspergillus fumigatus infection by inhibiting fungal conidia germination. This interaction involves host phosphoinositide 3-kinase and fungal lectin FleA, reducing virulence and preventing tissue invasion.
Area of Science:
- Medical Mycology
- Cell Biology
- Immunology
Background:
- Aspergillus fumigatus is an opportunistic fungal pathogen causing respiratory diseases, particularly in immunocompromised individuals.
- Fungal conidia are the infectious propagules that can reach the lower respiratory tract.
- Understanding host-pathogen interactions is crucial for managing fungal infections.
Purpose of the Study:
- To investigate the interaction between Aspergillus fumigatus conidia and bronchial epithelial cells.
- To characterize the mechanisms by which bronchial epithelial cells affect conidial germination.
- To identify host and fungal factors involved in this interaction.
Main Methods:
- Utilized the BEAS-2B cell line and primary human bronchial epithelial cells.
- Studied conidial germination of A. fumigatus laboratory and clinical strains using microscopic observation.
- Quantified fungal load via galactomannan measurements.
- Investigated the role of phosphoinositide 3-kinase pathway and fungal lectin FleA.
Main Results:
- Contact between bronchial epithelial cells and A. fumigatus conidia inhibited conidial germination.
- This fungistatic effect was independent of soluble factors or epithelial cell internalization.
- The inhibition involved the host phosphoinositide 3-kinase pathway and the fungal lectin FleA.
- Extracellular conidial germination inhibition prevents fungal filament formation and subsequent tissue invasion.
Conclusions:
- Bronchial epithelial cells play a protective role by attenuating A. fumigatus virulence.
- The interaction inhibits conidial germination, a critical step for fungal pathogenesis.
- This study elucidates a novel host-pathogen interaction mechanism involving specific signaling pathways and fungal molecules.
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