Targeting of phagolysosomes containing conidia of the fungus Aspergillus fumigatus with polymeric particles.
Appl Microbiol Biotechnol
; 107(2-3): 819-834, 2023 Feb.
Article
in En
| MEDLINE
| ID: mdl-36480041
ABSTRACT
Conidia of the airborne human-pathogenic fungus Aspergillus fumigatus are inhaled by humans. In the lung, they are phagocytosed by alveolar macrophages and intracellularly processed. In macrophages, however, conidia can interfere with the maturation of phagolysosomes to avoid their elimination. To investigate whether polymeric particles (PPs) can reach this intracellular pathogen in macrophages, we formulated dye-labeled PPs with a size allowing for their phagocytosis. PPs were efficiently taken up by RAW 264.7 macrophages and were found in phagolysosomes. When macrophages were infected with conidia prior to the addition of PPs, we found that they co-localized in the same phagolysosomes. Mechanistically, the fusion of phagolysosomes containing PPs with phagolysosomes containing conidia was observed. Increasing concentrations of PPs increased fusion events, resulting in 14% of phagolysosomes containing both conidia and PPs. We demonstrate that PPs can reach conidia-containing phagolysosomes, making these particles a promising carrier system for antimicrobial drugs to target intracellular pathogens. KEY POINTS ⢠Polymer particles of a size larger than 500 nm are internalized by macrophages and localized in phagolysosomes. ⢠These particles can be delivered to Aspergillus fumigatus conidia-containing phagolysosomes of macrophages. ⢠Enhanced phagolysosome fusion by the use of vacuolin1 can increase particle delivery.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aspergillus fumigatus
/
Phagosomes
Limits:
Humans
Language:
En
Journal:
Appl Microbiol Biotechnol
Year:
2023
Document type:
Article
Affiliation country:
Alemania