Playing ‘hide-and-seek’ with factor H: game-theoretical analysis of a single nucleotide polymorphism

Abstract

As a part of the complement system, factor H regulates phagocytosis and helps differentiate between a body's own and foreign cells. Owing to mimicry efforts, some pathogenic microorganisms such as are able to bind factor H on their cell surfaces and, thus, become similar to host cells. This implies that the decision between self and foreign is not clear-cut, which leads to a classification problem for the immune system. Here, two different alleles determining the binding affinity of factor H are relevant. Those alleles differ in the SNP Y402H; they are known to be associated with susceptibility to certain diseases. Interestingly, the fraction of both alleles differs in ethnic groups. The game-theoretical model proposed in this article explains the coexistence of both alleles by a game and investigates the trade-off between pathogen detection and protection of host cells. Further, we discuss the ethnicity-dependent frequencies of the alleles. Moreover, the model elucidates the mimicry efforts by pathogenic microorganisms.

Robustness during Aging—Molecular Biological and Physiological Aspects

“…One allele of the human complement factor H gene provides better protection against pathogenic bacteria and fungi but increases the risk to suffer later from age-related macula degeneration (AMD) [ 49 ]. This dilemma can be modeled by evolutionary game theory [ 50 ]. Since most wildlife animals die earlier than their life-span would allow, due to accidents, disease, starvation or predation, there has never been any evolutionary pressure on these pleiotropic effects [ 51 ].…”

Trends in mathematical modeling of host–pathogen interactions

“…If pathogen cells attain a quantitative advantage over host cells, even autoreactivity may occur. An alternative approach uses game theory [60]. It can nicely describe the tradeoff between auto-immunity (e.g., age-dependent macula degeneration) and susceptibility to bacterial infections as well as the dimorphism of the factor H gene.…”

“…Many processes can be described by alternative methods. For example, the interplay of alleles can often be described both by population genetics and game theory [60]. It depends on the aim of study which method is most suitable [26] or may be, to some extent, a matter of taste.…”

Identification of Antifungal Targets Based on Computer Modeling

“…In this way, a wide-range of parameters during the infection can be sampled by different rules and macrophage immune defense against Candida albicans delineated. As it allows to quantify how optimal the immune strategy is or where it is lacking, this has the potential to point to therapeutic options e.g., in immunocompromised patients including delineation of molecular targets such as factor H and modifications of it [ 186 ].…”