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.

Highlights

  • A virulent parasite that overcomes the immune system and kills its host may seem to have won the confrontation, but it is a Pyrrhic victory when the early death of the host reduces the probability of parasite transmission

  • We have shown that the IRG protein system essential for resistance against T. gondii infection in the mouse has a complex polymorphism on the scale of the MHC, and that at least one IRG haplotype, found in the wild-derived CIM strain mouse, is strikingly resistant to T. gondii strains that are highly virulent for laboratory mice

  • Our results suggest a selective explanation for the evolution of T. gondii strains that are highly virulent for certain mice

Read more

Summary

Introduction

A virulent parasite that overcomes the immune system and kills its host may seem to have won the confrontation, but it is a Pyrrhic victory when the early death of the host reduces the probability of parasite transmission. It is in the interests of all hosts and most parasites to prolong the encounter. Life or death outcomes for common infectious diseases in mammals are not generally determined by single, highly penetrant, polymorphic genes We here report such a case, involving infection of the house mouse, Mus musculus, with the ubiquitous intracellular protozoan parasite, Toxoplasma gondii. The probability that T. gondii completes its life cycle, which is roughly linear with duration of infection of the intermediate host, depends on early immune control

Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call