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

Musa A. Hassan, Aude Anais Olijnik, Eva Maria Frickel, Jeroen Saeij

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalInternational Journal for Parasitology
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Toxoplasma
Virulence
GTP Phosphohydrolases
Parasites
Immunity
Chromosomes, Human, Pair 11
Inbred Strains Mice
Vacuoles
Host-Parasite Interactions
Membranes
Interferon-gamma

Keywords

  • Host–parasite interactions
  • Mouse sub-species
  • ROP18
  • ROP5
  • Toxoplasma gondii
  • Wild-derived mice

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Clonal and atypical Toxoplasma strain differences in virulence vary with mouse sub-species. / Hassan, Musa A.; Olijnik, Aude Anais; Frickel, Eva Maria; Saeij, Jeroen.

In: International Journal for Parasitology, Vol. 49, No. 1, 01.01.2019, p. 63-70.

Research output: Contribution to journalArticle

Hassan, Musa A. ; Olijnik, Aude Anais ; Frickel, Eva Maria ; Saeij, Jeroen. / Clonal and atypical Toxoplasma strain differences in virulence vary with mouse sub-species. In: International Journal for Parasitology. 2019 ; Vol. 49, No. 1. pp. 63-70.
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AB - 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.

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