Genetic analysis of influences on survival following Toxoplasma gondii infection

Johnson, Jennifer J.; Suzuki, Yasuhiro; Mack, Douglas G.; Mui, Ernest; Estes, Randee; David, Chella S.; Skamene, Emil; Forman, James; McLeod, Rima

doi:10.1016/s0020-7519(01)00321-6

Cited by 49 publications

(50 citation statements)

References 25 publications

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“…Survival of mice and number of cysts were found to be regulated by several loci (14,15). These studies yielded valuable information on toxoplasmosis pathophysiology.…”

Section: Discussionmentioning

confidence: 96%

“…Parasites become encysted and persist in host tissues as dormant bradyzoites, as observed in the F 2 rats bearing two BN alleles at Toxo1 that develop a highly specific Ab response and brain cysts. The fact that not all rats show cysts in their brain is probably related to the relative resistance of BN rats to encystment (8), a trait likely to be under polygenic control (14,15). In contrast, F 2 rats homozygous for the LEW allele of Toxo1 show the characteristic LEW refractory state.…”

Section: Discussionmentioning

confidence: 99%

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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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“…Survival of mice and number of cysts were found to be regulated by several loci (14,15). These studies yielded valuable information on toxoplasmosis pathophysiology.…”

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

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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“…To date, little is known about differences in host susceptibility to T. gondii. There are earlier studies in mice that have shown that there are genetic influences that determine host susceptibility or resistance and some of the probable I921 I979 I978 I966 I954 I943 I9818 I9810 I9916 I9811 I0012 I0013 I9914 I0130 I0129 I0227 I0226 I0124 I0123 I0021 I0020 I0235 I0328 I0234 I0233 I0032 I0340 I0339 I0338 loci have been identified (Johnson et al 2002). However, it is not clear whether similar genetic influences are present within other species, including sheep.…”

Section: Discussionmentioning

confidence: 99%

Significant familial differences in the frequency of abortion and Toxoplasma gondii infection within a flock of Charollais sheep

et al. 2005

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A study was carried out to investigate the frequencies of abortion and congenital Toxoplasma gondii infection within 27 families (765 individuals) of a pedigree Charollais sheep flock maintained on a working farm in Worcestershire, UK, since 1992. Pedigree lambing records were analysed to establish the frequency of abortion for each family. The frequency of congenital infection was determined for each family by PCR analysis of tissue samples taken from newborn lambs. A total of 155 lambs were tested for congenital T. gondii infection, which were all born during the study period 2000–2003. Significant differences in the frequency of abortion between sheep families within this flock were observed with frequencies ranging between 0% and 48% (P<0·01). Significantly different infection frequencies with T. gondii were also observed for different families and ranged between 0% and 100% (P<0·01). Although the actual cause of each abortion was not verified, a highly significant positive correlation was found to exist between the frequency of abortion and the frequency of T. gondii infection in the same families (P<0·01). The data presented here raise further questions regarding the significance of congenital transmission of T. gondii within sheep populations, the possible successive vertical transmission of T. gondii within families of sheep, and the potential role of inherited genetic susceptibility to abortion with respect to T. gondii infection. This work invites further study into the epidemiology of ovine toxoplasmosis and may have implications for sheep husbandry methods in the future.

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“…This is explained in the case of schizophrenia by the possible participation of certain genes in its pathogeny [21], and in the case of toxoplasmosis by the possible common exposure of family members to the parasite, although a genetic influence has also been proposed [22].…”

Section: Epidemiologic Data On the Association Between Toxoplasmosis mentioning

confidence: 99%

Toxoplasma gondii and Schizophrenia: A Relationship That Is Not Ruled Out

Sorlózano-Puerto¹,

Gutiérrez‐Fernández²

2016

Schizophrenia Treatment - The New Facets

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Over recent years, it has been proposed that some diseases of unknown origin, such as schizophrenia, may be caused by persistent chronic infections coupled with a genetic component and may be perpetuated by the immune system. This hypothesis is supported by epidemiological and biological evidence on the exposure of schizophrenics to infectious diseases during prenatal or postnatal periods, including Toxoplasma gondii, chlamydia, human herpes virus, human endogenous retroviruses, parvovirus B19, mumps, and flu viruses. This growing list of microbes will undoubtedly continue to increase in the future. Linking infection to schizophrenia is a complex challenge that requires further experimental and epidemiological research. T. gondii is the infectious agent that has most frequently been related to neuropsychiatric disorders, including schizophrenia, and it is considered to represent a highly useful model to analyze the influence of a microorganism on human behavior and the development of psychiatric disease. It may also help to detect patient subpopulations susceptible to treatment with specific antimicrobials by improving definition of the differential phenotype of the disease, and it offers the possibility of a preventive approach.

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Genetic analysis of influences on survival following Toxoplasma gondii infection

Cited by 49 publications

References 25 publications

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

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

Significant familial differences in the frequency of abortion and Toxoplasma gondii infection within a flock of Charollais sheep

Toxoplasma gondii and Schizophrenia: A Relationship That Is Not Ruled Out

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