Speaker
Description
Candida albicans can cause life-threatening invasive infections, yet in an ex vivo human whole-blood infection model a substantial fraction of fungal cells remains extracellular despite the presence of phagocytes. Previous work suggested that fungal cells acquire host-derived surface markers via binding of neutrophil-derived extracellular vesicles (EV), reducing their uptake by immune cells.
To investigate the emergence of this immune-evasive phenotype, we extended a previously developed state-based virtual infection model of host–pathogen interactions \cite{hunniger_2014}. Specifically, we formulated two mechanistic models representing alternative hypotheses for the relationship between EV-decoration and immune evasion, where the immune evasion either (i) depends on the EV-decoration or (ii) occurs independently of it.
The decoration-dependent model overestimated the amount of free extracellular pathogens. In contrast, the decoration-independent mechanism best reproduced the data and predicted that ~40% of fungal cells first become EV-decorated and subsequently immune-evasive, whereas ~60% follow the reverse order. The predicted pathway distribution strongly depends on the time scale of decoration: if it occurs within minutes, nearly all fungal cells become EV-decorated prior to immune evasion, effectively reducing the system to the decoration-independent mechanism. The model predicts targeted follow-up experiments to discriminate between proposed mechanisms.
Bibliography
@article{hunniger_2014,
title = {A virtual infection model quantifies innate effector mechanisms and candida albicans immune escape in human blood},
volume = {10},
issn = {1553-7358},
url = {https://dx.plos.org/10.1371/journal.pcbi.1003479},
doi = {10.1371/journal.pcbi.1003479},
language = {en},
number = {2},
urldate = {2026-03-10},
journal = {PLoS Computational Biology},
author = {Hünniger, Kerstin and Lehnert, Teresa and Bieber, Kristin and Martin, Ronny and Figge, Marc Thilo and Kurzai, Oliver},
editor = {De Boer, Rob J.},
month = feb,
year = {2014},
pages = {e1003479},
}
