Abstract
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 responses 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 M. m. domesticus, M. m. musculus and M. m. 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 localising and subsequently vesiculating the parasitophorous vacuole membrane. However, despite the localization of known effector Irgs to the Toxoplasma parasitophorous vacuole membrane, we observed that some atypical Toxoplasma strains are virulent in all the mouse strains tested. The virulence of these atypical strains in M. m. musculus could not be attributed to individual rhoptry protein 5 (ROP5) alleles, a secreted parasite pseudokinase that antagonises the canonical effector Irgs and is indispensable for parasite virulence in laboratory inbred mice (M. m. 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.
Highlights
Toxoplasma is a ubiquitous obligate intracellular protozoan parasite that can infect virtually any nucleated vertebrate cell
No.: IJPara18_188R1), we present three main findings: 1) Virulence in Toxoplasma varies with parasite strains and mouse sub-species, 2) Resistance of Mus musculus musculus to the RH Toxoplasma strain is due to a penetrant locus on chromosome 11 and, 3) Toxoplasma strain difference in virulence in Mus musculus musculus is independent of individual alleles of the secreted pseudokinase, rhoptry protein 5 (ROP5)
We wondered if the differences in the virulence of RH in representative M. m. domesticus and M. m. castaneus strains was due to the known genetic diversity between the mouse sub-species or was restricted to immune factors unique to the CIM mouse
Summary
Toxoplasma is a ubiquitous obligate intracellular protozoan parasite that can infect virtually any nucleated vertebrate cell. Toxoplasma isolates in Europe and North America mostly belong to four clonal lineages, type I, II, III and 12 (Howe and Sibley, 1995; Khan et al, 2011). In South America, at least 150 genotypes (South American or atypical strains) that cluster into haplogroups 4 to 15 (Minot et al, 2012; Shwab et al, 2014; Su et al., 2012), have been isolated, but none of these are clonal. The factors that contributed to the genetic diversity in South America are emergent, some of these atypical strains have been associated with outbreaks of severe human toxoplasmosis (Carme et al, 2009, 2002).
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