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Title:   Author  item
                                            Dubey, Jitenderitem
                                            MCCONKEY, GLENN - University Of Leedsitem
                                            FERREIRA, LEANDRA - Former ARS Employeeitem
                                            ALSAAD, MOHAMMAD - University Of Leedsitem
                                            VERMA, SHIV - Orise Fellowitem
                                            ALVES, DERRON - The Joint Pathology Center (JPC)item
                                            HOLLAND, GARRY - Geffen School Of Medicine
  Submitted to: PLOS ONE
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/1/2016
                                    Publication  Date: 5/26/2016
                                    Citation: Dubey, J.P., Mcconkey, G.A., Ferreira, L., Alsaad, M., Verma, S.K., Alves, D.A., Holland, G.N. 2016. Experimental toxoplasmosis in rats induced orally with eleven strains of Toxoplasma gondii of seven genotypes: Tissue tropism, tissue cyst size, neural lesions, tissue cyst rupture without reactivation, and ocular lesions. PLoS One. doi: 10.1371/journal.pone.0156255.Interpretive Summary: Toxoplasmosis continues to be a public health problem worldwide. It causes mental retardation and loss of vision in children, and abortion in livestock. Cats are the main reservoir of T. gondii because they are the only hosts that can excrete the resistant stage (oocyst) of the parasite in the feces. Cats are thought to become infected mostly by eating tissues of infected rodents and birds. T. gondii reportedly manipulates rodent behavior so that infected rodents are losing fear of the cat so that they are easy prey for cats. The parasite encysted in different regions of rodent brain is thought to influence this behavior. However, most studies are based on highly susceptible rodent, the mouse. In the present investigation the authors reevaluated the rat model of toxoplasmosis using 11 strains of the parasite of different genotypes. They found that the parasite was distributed in all regions of the brain, including the eyes. The results will be of interest to biologists, parasitologists, and veterinarians, and to scientists who would like to study different aspects of toxoplasmosis in a laboratory model.
                                Technical Abstract: The protozoan parasite Toxoplasma gondii is one of the most widely distributed and most successful microorganism. Of all
warm blooded hosts, only cats can excrete the environmentally resistant stage, the oocyst. T. gondii manipulates rodent behavior so that infected rodents are losing fear of the cat. The parasite encysted in different regions of brain is thought to influence this behavior. However, most studies are based on highly a susceptible rodent, the mouse.

Methodology/Principal Findings: Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains, and 11 strains of different
genotypes) of same age, strain and sex, after oral inoculation with oocysts (natural route and natural stage of the parasite ingested) of T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether parasite genotype affects the distribution, location, tissue cyst size, and the lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall the colliculus was most highly infected although there was a large amount of variability with few rats considerably higher than the others. There was a statistically significant difference for the cerebellum, hypothalamus, and thalamus but this difference was not robust to Bonferroni multiple testing corrections. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities than the hypothalamus, subpallium, or hippocampus. The rhombencephalon had a higher density than the hypothalamus or subpallium. The hypothalamus was lower than most of the regions particularly the cerebral cortex, thalamus, cerebellum, rhombencephalon, and olfactory. Histologically, lesions were confined to brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammatory response in retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of –rats but not in myocardium and leg muscle.

Conclusion/significance: This study reevaluated in depth the rat model of toxoplasmosis and clarified many aspects of the biology of the parasite useful for future investigations.


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