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

J R Soc Interface. 2018 May;15(142):20170963. doi: 10.1098/rsif.2017.0963.

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 Candida albicans 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 battle of the sexes 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.

Keywords: battle of the sexes game; complement factor H; evolutionary game theory; innate immune system; molecular mimicry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Candida albicans
  • Candidiasis / genetics
  • Candidiasis / metabolism
  • Complement Factor H / genetics
  • Complement Factor H / metabolism
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Models, Biological*
  • Polymorphism, Single Nucleotide*

Substances

  • CFH protein, human
  • Complement Factor H