Reciprocal virulence and resistance polymorphism in the relationship between Toxoplasma gondii and the house mouse

Elife. 2013 Oct 29:2:e01298. doi: 10.7554/eLife.01298.

Abstract

Virulence in the ubiquitous intracellular protozoon Toxoplasma gondii for its natural intermediate host, the mouse, appears paradoxical from an evolutionary standpoint because death of the mouse before encystment interrupts the parasite life cycle. Virulent T. gondii strains secrete kinases and pseudokinases that inactivate the immunity-related GTPases (IRG proteins) responsible for mouse resistance to avirulent strains. Such considerations stimulated a search for IRG alleles unknown in laboratory mice that might confer resistance to virulent strains of T. gondii. We report that the mouse IRG system shows extraordinary polymorphic complexity in the wild. We describe an IRG haplotype from a wild-derived mouse strain that confers resistance against virulent parasites by interference with the virulent kinase complex. In such hosts virulent strains can encyst, hinting at an explanation for the evolution of virulence polymorphism in T. gondii. DOI:http://dx.doi.org/10.7554/eLife.01298.001.

Keywords: IRG proteins; Mouse; Other; Toxoplasma gondii; coevolution; virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Wild / genetics*
  • Animals, Wild / immunology
  • Animals, Wild / parasitology
  • Binding Sites
  • Biological Evolution
  • Genetic Loci
  • Haplotypes
  • Host-Parasite Interactions
  • Hydro-Lyases / chemistry
  • Hydro-Lyases / genetics*
  • Hydro-Lyases / metabolism
  • Mice
  • Models, Molecular
  • Polymorphism, Genetic
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Kinases / chemistry
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism
  • Toxoplasma / genetics*
  • Toxoplasma / immunology
  • Toxoplasma / pathogenicity
  • Toxoplasmosis, Animal / genetics*
  • Toxoplasmosis, Animal / immunology
  • Toxoplasmosis, Animal / parasitology
  • Virulence / genetics

Substances

  • Protein Isoforms
  • Protozoan Proteins
  • Protein Kinases
  • Hydro-Lyases
  • Irg1 protein, mouse

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.