Molecular mimicry is the formation of specific molecules by microbial pathogens to avoid recognition and attack by the immune system of the host. Several pathogenic Ascomycota and Zygomycota show such a behaviour by utilizing human complement factor H to hide in the blood stream. We call this type of mimicry molecular crypsis. Such a crypsis can reach a point where the immune system can no longer clearly distinguish between self and non-self cells. Thus, a trade-off between attacking disguised pathogens and erroneously attacking host cells has to be made. Based on signalling theory and protein-interaction modelling, we here present a mathematical model of molecular crypsis of pathogenic fungi using the example of Candida albicans. We tackle the question whether perfect crypsis is feasible, which would imply that protection of human cells by complement factors would be useless. The model identifies pathogen abundance relative to host cell abundance as the predominant factor influencing successful or unsuccessful molecular crypsis. If pathogen cells gain a (locally) quantitative advantage over host cells, even autoreactivity may occur. Our new model enables insights into the mechanisms of candidiasis-induced sepsis and complement-associated autoimmune diseases.
SEEK ID: https://funginet.hki-jena.de/publications/175
PubMed ID: 30779817
Journal: PLoS One
Citation: PLoS One. 2019 Feb 19;14(2):e0212187. doi: 10.1371/journal.pone.0212187. eCollection 2019.
Date Published: 20th Feb 2019
Authors: S. N. Lang, S. Germerodt, C. Glock, Christine Skerka, Peter Zipfel, Stefan Schuster
Created: 18th Feb 2021 at 09:47