On the determination of Toxoplasma gondii virulence in mice

Saraf, Pooja; Shwab, E. Keats; Dubey, J. P.; Su, Chunlei

doi:10.1016/j.exppara.2017.01.009

Cited by 68 publications

(76 citation statements)

References 42 publications

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“…1) and B1 gene-analysis verified that low ME49EW1 cyst counts in brain were not the result of a change in Toxoplasma distribution in mouse tissues. The loss of developmental competency following forced adaptation to HFF cell culture is not an isolated outcome (10). Infection of CBA/j mice with two common laboratory strains (10,000 tachyzoites, i.p.)…”

Section: Adaptation To Cell Culture Leads To Loss Of Toxoplasma Develmentioning

confidence: 99%

An ex vivo model ofToxoplasmarecrudescence

Goerner

Vizcarra

Hong

et al. 2020

Preprint

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Efforts to develop therapies against Toxoplasma reactivation have been hampered by the lack of an in vitro model of bradyzoite recrudescence. To overcome this issue, we established a new ex vivo model of bradyzoite recrudescence using bradyzoites from an unadapted Type II ME49 strain isolated from murine brain tissue to infect human foreskin fibroblasts and neonatal murine astrocytes. Bradyzoite infection of both host cell types produced two sequential tachyzoite growth stages that appeared similar to previous sporozoite in vitro infections; a fast-growing stage was followed by spontaneous formation of a slowergrowing stage. In astrocytes, but not in fibroblasts, there was evidence of second bradyzoite to bradyzoite recrudescent pathway that occurred simultaneously with the bradyzoite to tachyzoite pathway.Thus, the host cell environment strongly influenced the pathway of bradyzoite recrudescence. Infections of mice with either the fast-growing or slow-growing recrudescent tachyzoites showed progressive decreases in brain cyst formation that could be fully recovered using serial tissue cyst passage demonstrating the loss of developmental capacity was reversible. By contrast, poor tissue cyst formation of laboratory-adapted tachyzoites was not reversible by these approaches indicating developmental incompetence was permanent in these strains. In order to develop methods to distinguish strain developmental competency, we identified Toxoplasma genes highly expressed in ME49EW in vivo tissue cysts and developed a qPCR approach that differentiates immature from mature bradyzoites. In summary, the results presented describe a new ex vivo bradyzoite recrudescence model that fully captures the reported growth and developmental processes observed during toxoplasmosis reactivation in vivo opening the door to the further study of these important features of the Toxoplasma intermediate life cycle.

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Section: Adaptation To Cell Culture Leads To Loss Of Toxoplasma Develmentioning

confidence: 99%

An ex vivo model ofToxoplasmarecrudescence

Goerner

Vizcarra

Hong

et al. 2020

Preprint

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“…Los animales susceptibles presentan diferentes signos clínicos como trastornos neuromusculares en caninos, aborto en pequeños rumiantes, natimortos en porcinos y toxoplasmosis fatal en marsupiales australianos y monos del Nuevo Mundo (Dubey, 2010). Los ratones de laboratorio (Mus musculus) son sensibles a la infección y son en general usados como el modelo de referencia para evaluar la virulencia del parásito (Saraf et al, 2017). En salud humana los signos clínicos de infección incluyen lesiones retinianas (toxoplasmosis ocular), lesiones del sistema nervioso central (principalmente asociadas con toxoplasmosis congénita) y falla multisistémica en individuos inmunocomprometidos (Weiss & Kim, 2014).…”

Section: Ciclo De Vida E Infecciónunclassified

“…El ratón (Mus musculus) ha sido utilizado como el modelo principal para evaluar virulencia de T. gondii (Saraf et al, 2017). La virulencia en ratones depende de varios factores: el estadio del parásito, la ruta de inoculación, la dosis, el genotipo de T. gondii, el número de pasajes del parásito en cultivo celular o ratón y las cepas de ratones utilizados (Dubey et al, 2004).…”

Section: Antecedentes De Ensayos En Modelo Murinounclassified

“…La virulencia en ratones depende de varios factores: el estadio del parásito, la ruta de inoculación, la dosis, el genotipo de T. gondii, el número de pasajes del parásito en cultivo celular o ratón y las cepas de ratones utilizados (Dubey et al, 2004). La variabilidad entre estos factores dificulta la comparación de resultados (Saraf et al, 2017). La virulencia de diversos aislamientos de T. gondii en ratón parecería estar correlacionada con los signos clínicos de la toxoplasmosis en humanos (Xiao & Yolken, 2015).…”

Section: Antecedentes De Ensayos En Modelo Murinounclassified

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Congenital human toxoplasmosis caused by non-clonal Toxoplasma gondii genotypes in Argentina

Pardini

Bernstein

Carral

et al. 2019

Parasitology International

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“…Mice as intermediate hosts are extensively used for pathogenesis and vaccine study of toxoplas-mosis, in which high numbers of tachyzoites of T. gondii (RH) (10 3 , 10 4 , 10 5 ) have been used [5][6][7][8][9][10][11][12]. T. gondii (RH) is highly virulent and its infection in mice causes death [13]. Mice infected with 10 5 tachyzoites show no CD8 + T and germinal center B cell responses from the spleen at day 16 post-infection, since these immune cells are largely damaged [12].…”

mentioning

confidence: 99%

Parasite Infiltration and Apoptosis in Spleen upon Toxoplasma gondii Infection

2019

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Toxoplasma gondii infection induces parasite infiltration and apoptosis in the spleen. However, dose-dependent parasite infiltration, apoptosis, body weight alternations and survival in mice remain largely unknown. In this study, mice were intraperitoneally infected with 10, 30 or 100 tachyzoites of T. gondii, respectively. Parasite infiltration and apoptosis in the spleen were analyzed on days 3, 7, and 9 post-infection by immunohistochemistry and flow cytometry. Significantly higher levels of T. gondii infiltration and apoptosis in the spleen were found in 30 and 100 tachyzoites infected mice compared to 10 tachyzoites infected mice on days 7 and 9 post-infection. Although 30 and 100 tachyzoites infected mice showed significant body weight loss compared to 10 tachyzoites infected mice, all of the 100, 30, and 10 tachyzoites infected mice died by days 12, 15, and 17, each respectively. Interestingly, T. gondii infiltration in 10 tachyzoites infected mice were limited to capsule area of the spleen on day 9 post-infection. Several areas of parasite infiltrations were found in the 30 tachyzoites infected mice, where noticeable levels of splenic capsule de-adhesion occurred. These results indicated that parasite infiltration and apoptosis in the spleen, as well as body weight loss (survival) are closely correlated with infection dosage. The level of T. gondii infiltration and apoptosis in the spleen and splenic de-adhesion were dependent on the parasite dose.

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On the determination of Toxoplasma gondii virulence in mice

Cited by 68 publications

References 42 publications

An ex vivo model ofToxoplasmarecrudescence

An ex vivo model ofToxoplasmarecrudescence

Congenital human toxoplasmosis caused by non-clonal Toxoplasma gondii genotypes in Argentina

Parasite Infiltration and Apoptosis in Spleen upon Toxoplasma gondii Infection

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