Clonal and atypical Toxoplasma strain differences in virulence varies with mouse sub-species

The severe virulence of Toxoplasma gondii in classical
laboratory inbred mouse strains contradicts the hypothesis that house
mice (Mus musculus) are the most important intermediate hosts for its
transmission and evolution because death of the mouse before parasite
transmission equals death of the parasite. However, the classical
laboratory inbred mouse strains (Mus musculus domesticus), commonly used
to test Toxoplasma strain differences in virulence, do not capture the
genetic diversity within Mus musculus. Thus, it is possible that
Toxoplasma strains that are severely virulent in laboratory inbred mice
are avirulent in some other mouse sub-species. Here, we present insight
into the response of individual mouse strains, representing strains of
the genetically divergent Mus musculus musculus, Mus musculus castaneus
and Mus musculus domesticus, to infection with individual clonal and
atypical Toxoplasma strains. We observed that, unlike Mus musculus
domesticus¬, Mus musculus musculus and Mus musculus castaneus are
resistant to the clonal Toxoplasma strains. For M. m. musculus, we show
that this is due to a locus on chromosome 11 that includes the genes that
encode the interferon gamma (IFNG)-inducible immunity-related GTPases
(Irgs) that can kill the parasite by localizing and subsequently
vesiculating the parasitophorous vacuole membrane (PVM). However, despite
the localization of known effector Irgs to the Toxoplasma PVM, we
observed that some atypical Toxoplasma strains are virulent in all the
mouse strains tested. The virulence of these atypical strains in Mus
musculus musculus could not be attributed to individual rhoptry protein 5
(ROP5) alleles, a secreted parasite pseudokinase that antagonizes the
canonical effector IRGs and is indispensable for parasite virulence in
laboratory inbred mice (Mus musculus domesticus). We conclude that murine
resistance to Toxoplasma is modulated by complex interactions between
host and parasite genotypes and may be independent of known effector Irgs
on murine chromosome 11.