Molecular crypsis by pathogenic fungi using human factor H. A numerical model
Stefan N Lang1, Sebastian Germerodt1, Christina Glock1
1Dept. of Bioinformatics, Friedrich Schiller University Jena, Jena, Germany.
Abstract:
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.
Insights
Pathogenic fungi use molecular crypsis to evade the immune system by mimicking host molecules. This study models fungal molecular crypsis, revealing pathogen abundance is key to immune evasion and potential autoimmune responses.
Area of Science:
- Microbiology
- Immunology
- Computational Biology
Background:
- Pathogenic fungi employ molecular mimicry to evade host immune responses.
- Molecular crypsis, using host complement factor H, allows fungi like Candida albicans to hide in the bloodstream.
- This immune evasion can blur the distinction between self and non-self, posing a challenge for host defense.
Purpose of the Study:
- To investigate the feasibility of perfect molecular crypsis in pathogenic fungi.
- To develop a mathematical model for molecular crypsis using Candida albicans as an example.
- To understand the factors influencing the success or failure of fungal molecular crypsis.
Main Methods:
- Utilized signalling theory and protein-interaction modeling.
- Developed a mathematical model to simulate molecular crypsis.
- Analyzed the relationship between pathogen and host cell abundance.
Main Results:
- Pathogen abundance relative to host cell abundance is the primary determinant of molecular crypsis success.
- High pathogen loads can lead to a breakdown of immune self/non-self discrimination.
- Autoreactivity may occur when pathogen cells outnumber host cells.
Conclusions:
- Perfect molecular crypsis is not always feasible, as immune evasion depends on pathogen-host cell ratios.
- The model provides insights into candidiasis-induced sepsis.
- The findings contribute to understanding complement-associated autoimmune diseases.
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