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

Luke D. Halder, Svitlana Babych, Diana I. Palme, Elham Mansouri-Ghahnavieh, Lia Ivanov, Victory Ashonibare, Daniela Langenhorst, Bhupesh Prusty, Günter Rambach, Melissa Wich, Nora Trinks, Matthew G. Blango, Daniel Kornitzer, Ulrich Terpitz, Cornelia Speth, Berit Jungnickel, Niklas Beyersdorf, Peter F. Zipfel, Axel A. Brakhage, Christine Skerka

Research output: Contribution to journalArticlepeer-review

Abstract

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. IMPORTANCE Over the last decade, communication between immune cells by extracellular vesicle-associated miRNAs has emerged as an important regulator of the coordinated immune response. Therefore, a thorough understanding of the conversation occurring via miRNAs, especially during infection, may provide novel insights into both the host reaction to the microbe as well as the microbial response. This study provides evidence that the pathogenic fungus C. albicans communicates with human monocytes and induces the release of a human miRNA that promotes fungal growth. This mechanism represents an unexpected cross-species interaction and implies that an inhibition of specific miRNAs offers new possibilities for the treatment of human fungal infections.

Original languageEnglish
Article numbere03563
Pages (from-to)e0356321
JournalmBio
Volume13
Issue number1
DOIs
StatePublished - 8 Feb 2022

Keywords

  • CR1
  • CR3
  • Candida albicans
  • Extracellular vesicles
  • Host-pathogen interaction
  • Hsa-miR-21-5p
  • Hsa-miR-24-3p
  • Immune mechanisms
  • Immune response
  • MiRNA
  • Monocytes
  • TLR4

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Virology

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