Innate Refractoriness of the Lewis Rat to Toxoplasmosis Is a Dominant Trait That Is Intrinsic to Bone Marrow-Derived Cells

Sergent, Véronique; Cautain, Bastien; Khalife, Jamal; Deslée, Didier; Bastien, Patrick; Dao, Anne; Dubremetz, Jean‐François; Fournié, Gilbert J.; Saoudi, Abdelhadi; Cesbron-Delauw, Marie-France

doi:10.1128/iai.73.10.6990-6997.2005

Cited by 40 publications

(61 citation statements)

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“…For example, type I strains, which are highly virulent in mice, are not pathogenic in rats which developed a subclinical chronic infection. Some rat strains, such as the Lewis rat, are even refractory to infection with a mouse-highly virulent strain (Sergent et al, 2005). The genetic background in a given species, as demonstrated in different mouse strains, may also influence the expression of virulence.…”

Section: Th Emop August 2008mentioning

confidence: 99%

Toxoplasma gondii, “new” genotypes and virulence

Dardé¹

2008

Parasite

144

111

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Summary :Toxoplasma gondii has been described as a parasite with a low genetic diversity and a clonal population structure. The three main clonal lineages designated as type I, II or III largely predominate in Europe and North America. But strains not related to these main lineages circulate, notably, in other continents. They possess a shuffled combination of alleles that typify the three clonal types and unique polymorphisms detected by multilocus analysis. The population structure of Toxoplasma in these continents is also characterized by a higher genetic diversity associated with a lower linkage desequilibrium suggesting a role for genetic exchange. Due to their genomic diversity, it is difficult to draw global conclusions about their virulence. However, most of them are virulent in mice at isolation. Several reports also suggest a higher pathogenicity in humans and an association with ocular toxoplasmosis or severe cases of acquired toxoplasmosis in immunocompetent patients. T he three main types respond to the criteria for a clonal population structure of Toxoplasma (isolation of identical multilocus genotypes over large geographic areas and at interval of several years, and a strong linkage disequilibrium) (Tibayrenc et al., 1991). This simple clonal structure is accompanied by a low genetic divergence between the three main lineages (only ≈ 2 % divergence at the DNA sequence level between lineages). A large majority (84 %) of the of the single nucleotide polymorphisms (SNPs) identified among the three types are type I and II SNPs, type III polymorphisms (only 16 %) being located mainly on chromosome IV (Boyle et al., 2006). The assymetrical distribution of SNPs on chromosomes indicates that types I and III are second and first generation offspring, respectively, of a cross between a type II strain and one of two ancestral strains. The limited genetic diversity within each of these lineages and the low divergence between lineages strongly suggest that these three clonal lineages have expanded as the dominant strains relatively recently, from a common ancestor 10,000 years ago (Su et al., 2003).

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Section: Th Emop August 2008mentioning

confidence: 99%

Toxoplasma gondii, “new” genotypes and virulence

Dardé¹

2008

Parasite

144

111

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“…Indeed, unlike susceptible BN and F344 rats, LEW rats do not show trace of parasitic infection as shown by negative serology and lack of brain cysts. F 1 hybrid (LEW ϫ BN) and (LEW ϫ F344) rats are resistant to T. gondii, indicating a dominant effect of the involved gene(s) (9). We carried out genetic studies in LEW and BN rats, which are two extreme strains from an immunological point of view (10).…”

mentioning

confidence: 99%

The ratToxo1locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms

Cavaillès

Sergent

Bisanz

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Toxoplasmosis is a healthcare problem in pregnant women and immunocompromised patients. Like humans, rats usually develop a subclinical chronic infection. LEW rats exhibit total resistance to Toxoplasma gondii infection, which is expressed in a dominant mode. A genome-wide search carried out in a cohort of F 2 progeny of susceptible BN and resistant LEW rats led to identify on chromosome 10 a major locus of control, which we called Toxo1. Using reciprocal BN and LEW lines congenic for chromosome 10 genomic regions from the other strain, Toxo1 was found to govern the issue of T. gondii infection whatever the remaining genome. Analyzes of rats characterized by genomic recombination within Toxo1, reduced the interval down to a 1.7-cM region syntenic to human 17p13. In vitro studies showed that the Toxo1-mediated refractoriness to T. gondii infection is associated with the ability of the macrophage to impede the proliferation of the parasite within the parasitophorous vacuole. In contrast, proliferation was observed in fibroblasts whatever the genomic origin of Toxo1. Furthermore, ex vivo studies indicate that macrophage controls parasitic infection spreading by a Toxo1-mediated mechanism. This forward genetics approach should ultimately unravel a major pathway of innate resistance to toxoplasmosis and possibly to other apicomplexan parasitic diseases.T he protozoan Toxoplasma gondii is an obligate intracellular parasite that infects humans and a broad spectrum of vertebrate hosts. It is found worldwide, and the infection is common as indicated by a high prevalence of specific Ab among almost all human populations. T. gondii infection occurs by oral ingestion of either cysts from infected animal tissues, or oocysts excreted by cats. In healthy individuals, T. gondii establishes a chronic asymptomatic infection characterized by a specific immune response and the encystment of dormant bradyzoites into host tissues. A serious threat to human health can occur under congenital infection or reactivation of a latent infection in immunodeficient patients (1).Epidemiological studies have indicated that the genetic make-up of the host and of the parasite are involved in the phenotypic expression of toxoplasmosis (2-4). Genetic studies in humans are hampered by both population heterogeneity and environment variability. In experimental conditions, genetic and environmental factors are under control. Results from genetic studies in animal models can be applied to human pathology through comparative genomics (5, 6). Rats, like humans, usually develop subclinical toxoplasmosis (7); this contrasts with the severity of the disease developed in most strains of mice. Surprisingly, the LEW rat strain exhibits a complete resistance to Toxoplasma infection (8). Indeed, unlike susceptible BN and F344 rats, LEW rats do not show trace of parasitic infection as shown by negative serology and lack of brain cysts. F 1 hybrid (LEW ϫ BN) and (LEW ϫ F344) rats are resistant to T. gondii, indicating a dominant effect of the involved gene(s) (9). W...

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“…However, it is difficult to detect small cysts among brain aggregated components. The in situ enzymatic detection of bgalactosidase in Toxoplasma expressing the b-gal gene has been used to improve cyst numeration (8,9). This published method is, however, limited to b-gal transgenic parasites.…”

Section: Resultsmentioning

confidence: 99%

“…Aliquots of this suspension were used for rat and mouse oral infections. One month later, blood was collected from retro-orbital sinus for the detection of anti-Toxoplasma antibody response by immunofluorescence (9). Brains were then recovered 2 months pi and homogenized in PBS as described below.…”

Section: Parasites and Infectionmentioning

confidence: 99%

“…After one wash in PBS, the pellet was suspended in 4 ml of PBS and frozen in liquid nitrogen for 15 min then warmed at 378C to breakdown the cerebral tissue. Cysts were labelled with b-galactosidase reagents (9). Following one night of incubation at 378C, the suspension was distributed into four wells of six-well culture plates and scanned by light microscopy (magnification 3200) to count the blue-stained cysts.…”

Section: Parasites and Infectionmentioning

confidence: 99%

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Development of high‐throughput methods to quantify cysts of Toxoplasma gondii

et al. 2011

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Toxplasma is a protozoan parasite, which forms persistent cysts in tissues of chronically infected animals and humans. Cysts can reactivate leading to severe pathologies. They also contribute to the transmission of Toxoplasma infection in humans by ingestion of undercooked meat. Classically, the quantification of cyst burden in tissues uses microscopy methods, which are laborious and time consuming. Here, we have developed automated protocols to quantify cysts, based on flow cytometry or high-throughput microscopy. Brains of rodents infected with cysts of Prugniaud strain were incubated with the FITC-Dolichos biflorus lectin and analyzed by flow cytometry and high-throughput epifluorescence microscopy. The comparison of cyst counts by manual epifluorescence microscopy to flow cytometry or to highthroughput epifluorescence microscopy revealed a good correlation (r 5 0.934, r 5 0.993, P \ 0.001 respectively). High-throughput epifluorescence microscopy was found to be more specific and sensitive than flow cytometry and easier to use for large series of samples. This reliable and easy protocol allow the specific detection of Toxoplasma cysts in brain, even at low concentrations; it could be a new way to detect them in water and in contaminate food. ' 2011 International Society for Advancement of Cytometry

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Innate Refractoriness of the Lewis Rat to Toxoplasmosis Is a Dominant Trait That Is Intrinsic to Bone Marrow-Derived Cells

Cited by 40 publications

References 32 publications

Toxoplasma gondii, “new” genotypes and virulence

Toxoplasma gondii, “new” genotypes and virulence

The ratToxo1locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms

Development of high‐throughput methods to quantify cysts of Toxoplasma gondii

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