Molecular crypsis by pathogenic fungi using human factor H. A numerical model

Abstract

Molecular mimicry is the formation of specic molecules by microbial pathogens to avoid recognition and attack by the immune system of the host. Several pathogenic Ascomycota and Zygomycota show a similar 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-o between attacking host cells and mimicking pathogens has to be made, which can lead to autoreactivity. 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. The model identies pathogen abundance relative to host cell abundance as the predominant factor inuencing 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.