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Candida albicans Induces Cross-Kingdom miRNA Trafficking in Human Monocytes To Promote Fungal Growth

In response to infections, human immune cells release extracellular vesicles (EVs) that carry a situationally adapted cocktail of proteins and nucleic acids, including microRNAs (miRNAs), to coordinate the immune response. In this study, we identified hsa-miR-21-5p and hsa-miR-24-3p as the most comm...

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Detalles Bibliográficos
Autores principales: Halder, Luke D., Babych, Svitlana, Palme, Diana I., Mansouri-Ghahnavieh, Elham, Ivanov, Lia, Ashonibare, Victory, Langenhorst, Daniela, Prusty, Bhupesh, Rambach, Günter, Wich, Melissa, Trinks, Nora, Blango, Matthew G., Kornitzer, Daniel, Terpitz, Ulrich, Speth, Cornelia, Jungnickel, Berit, Beyersdorf, Niklas, Zipfel, Peter F., Brakhage, Axel A., Skerka, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822622/
https://www.ncbi.nlm.nih.gov/pubmed/35132877
http://dx.doi.org/10.1128/mbio.03563-21
Descripción
Sumario:In response to infections, human immune cells release extracellular vesicles (EVs) that carry a situationally adapted cocktail of proteins and nucleic acids, including microRNAs (miRNAs), to coordinate the immune response. In this study, we identified hsa-miR-21-5p and hsa-miR-24-3p as the most common miRNAs in exosomes released by human monocytes in response to the pathogenic fungus Candida albicans. Functional analysis of miRNAs revealed that hsa-miR-24-3p, but not hsa-miR-21-5p, acted across species and kingdoms, entering C. albicans and inducing fungal cell growth by inhibiting translation of the cyclin-dependent kinase inhibitor Sol1. Packaging of hsa-miR-24-3p into monocyte exosomes required binding of fungal soluble β-glucan to complement receptor 3 (CR3) and binding of mannan to Toll-like receptor 4 (TLR4), resulting in receptor colocalization. Together, our in vitro and in vivo findings reveal a novel cross-species evasion mechanism by which C. albicans exploits a human miRNA to promote fungal growth and survival in the host.