Human neutrophils release extracellular RNA that modulates Aspergillus fumigatus gene expression across kingdoms.
- 1Leibniz Institute for Natural Product Research and Infection Biology: Hans Knoell Institute
Abstract
Extracellular RNAs (exRNAs) are emerging as potent bidirectional interkingdom effectors of host-pathogen interactions, particularly in plant and insect systems. Here, using small RNA-sequencing and genetic manipulation, we provide evidence consistent with a function of the human neutrophil exRNA-ome in modulating gene expression across kingdoms in the fungal pathogen Aspergillus fumigatus. The neutrophil extracellular space contains a diverse repertoire of RNA, which was corroborated using a droplet-digital stem-loop RT-PCR protocol to measure differential abundance of several tRNA-derived RNAs between two extracellular fractions. A closer inspection of the extracellular miRNA pool revealed enrichment of antimicrobial Let-7 family sRNAs and immunomodulatory miR-223, among others. Secretion of these sRNAs was largely impervious to infection status, suggesting that neutrophils produce and maintain an antimicrobial exRNA environment against A. fumigatus that requires further targeting. Cross-kingdom miRNA target prediction and exRNA delivery experiments revealed that putative fungal targets are modulated independently of the fungal argonaute proteins and in a donor-dependent manner. Although heterogeneous, for donors that exhibited a silencing effect, mutated target sequences in the fungus did reverse silencing. We hypothesize that the exRNA landscape produced by neutrophils contributes to their multifaceted role in antifungal defense.
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BibTeX
@misc{bruch2026human,
title = {{Human neutrophils release extracellular RNA that modulates Aspergillus fumigatus gene expression across kingdoms.}},
author = {A. Bruch and L. Schrettenbrunner and B. Israni and E. Boehm and X. Pan and C. Visser and T. Orasch and A. A. Brakhage and M. G. Blango},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.758605},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.758605v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Human neutrophils release extracellular RNA that modulates Aspergillus fumigatus gene expression across kingdoms.
AU - A. Bruch
AU - L. Schrettenbrunner
AU - B. Israni
AU - E. Boehm
AU - X. Pan
AU - C. Visser
AU - T. Orasch
AU - A. A. Brakhage
AU - M. G. Blango
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.758605
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.758605v1
AB - Extracellular RNAs (exRNAs) are emerging as potent bidirectional interkingdom effectors of host-pathogen interactions, particularly in plant and insect systems. Here, using small RNA-sequencing and genetic manipulation, we provide evidence consistent with a function of the human neutrophil exRNA-ome in modulating gene expression across kingdoms in the fungal pathogen Aspergillus fumigatus. The neutrophil extracellular space contains a diverse repertoire of RNA, which was corroborated using a droplet-digital stem-loop RT-PCR protocol to measure differential abundance of several tRNA-derived RNAs between two extracellular fractions. A closer inspection of the extracellular miRNA pool revealed enrichment of antimicrobial Let-7 family sRNAs and immunomodulatory miR-223, among others. Secretion of these sRNAs was largely impervious to infection status, suggesting that neutrophils produce and maintain an antimicrobial exRNA environment against A. fumigatus that requires further targeting. Cross-kingdom miRNA target prediction and exRNA delivery experiments revealed that putative fungal targets are modulated independently of the fungal argonaute proteins and in a donor-dependent manner. Although heterogeneous, for donors that exhibited a silencing effect, mutated target sequences in the fungus did reverse silencing. We hypothesize that the exRNA landscape produced by neutrophils contributes to their multifaceted role in antifungal defense.
ER -