The liver as an organ at risk for<i>Toxoplasma</i>transmission during transplantation: myth or reality?

Autier, Brice; Dion, Sarah; Robert‐Gangneux, Florence

doi:10.1136/jclinpath-2018-205066

Cited by 18 publications

(11 citation statements)

References 24 publications

(11 reference statements)

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“…Since Imiquimod induces interconversion between brain stages, it is likely contraindicated in immunocompromised patients, despite the total abrogation of reactivation in 50% of treated mice. However, these results create an important application in solid organ transplantation where pre-treatment of transplanted organs will reduce the chances of infection, especially that the risk of infection with T. gondii, in heart, liver, kidney, and bone marrow transplantation is still extremely high (82)(83)(84). A strain depleted from Profilin is refractory to treatment with Imiquimod ( Figure 4A), and TLR-12 expression levels in cells infected with this parasite line remained unchanged ( Figure 4B).…”

Section: Discussionmentioning

confidence: 99%

Imiquimod Targets Toxoplasmosis Through Modulating Host Toll-Like Receptor-MyD88 Signaling

et al. 2021

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Toxoplasma gondii is a prevalent parasite of medical and veterinary importance. Tachyzoïtes and bradyzoïtes are responsible for acute and chronic toxoplasmosis (AT and CT), respectively. In immunocompetent hosts, AT evolves into a persistent CT, which can reactivate in immunocompromised patients with dire consequences. Imiquimod is an efficient immunomodulatory drug against certain viral and parasitic infections. In vivo, treatment with Imiquimod, throughout AT, reduces the number of brain cysts while rendering the remaining cysts un-infectious. Post-establishment of CT, Imiquimod significantly reduces the number of brain cysts, leading to a delay or abortion of reactivation. At the molecular level, Imiquimod upregulates the expression of Toll-like receptors 7, 11, and 12, following interconversion from bradyzoïtes to tachyzoïtes. Consequently, MyD88 pathway is activated, resulting in the induction of the immune response to control reactivated Toxoplasma foci. This study positions Imiquimod as a potent drug against toxoplasmosis and elucidates its mechanism of action particularly against chronic toxoplasmosis, which is the most prevalent form of the disease.

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Section: Discussionmentioning

confidence: 99%

Imiquimod Targets Toxoplasmosis Through Modulating Host Toll-Like Receptor-MyD88 Signaling

et al. 2021

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“…Toxoplasmosis following LT is uncommon. During a period of 40 years, only 31 cases have been reported, and of these only 10 were the consequence of donor-to-recipient mismatch [24]. As a result, prophylaxis is sporadically prescribed by transplant physicians, despite life-threatening cases of post-transplant toxoplasmosis having been described [24].…”

Section: Discussionmentioning

confidence: 99%

“…Although clinically overt toxoplasmosis has been reported in a lower number of liver transplant (LT) recipients than in heart and kidney transplant patients, it can be fatal [24] with reactivation of latent infection being the leading cause of TG-related morbidity and mortality after LT [5,15].…”

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii Monitoring in Liver Transplantation Patients: A Single Center Cross-Sectional Study in an Italian Hospital

et al. 2020

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Toxoplasma gondii (TG) is one of the most widespread intracellular parasites in the world, despite the slight declining trend in industrialized countries. Whilst the infection is often asymptomatic in immunocompetent hosts, in immunocompromised patients such as organ transplant recipients it can have important clinical sequels with even fatal consequences. We retrospectively reviewed 568 primary liver transplants (LT) from deceased donors from 2012 to 2017. Data were analyzed adjusting for year, gender, and age. The study objective was to assess the incidence of post-transplant TG infection and adherence to international guidelines for primary chemoprophylaxis. Prior to transplantation, 42.4% of recipients tested seronegative and 56.5% seropositive, while 36.6% of donors were seropositive and 40.4% showed undetermined serology. Anti-TG antibody titer was higher in patients born abroad (71.4%) versus Italy (54.8%). Among recipients at high risk of post-transplant TG infection, 82.7% of them received chemoprophylaxis, while in 17.3% of cases no prophylaxis was administered. At a mean (SD) follow-up of 21.2 (12.4) months no case of TG infection has been observed. Despite the low rate of adherence to recommendations, prophylaxis of high-risk LT recipients provides control of post-transplant TG infection risk. Review of current guidelines is warranted for low-risk populations.

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“…However, an important caveat with these studies is that they were performed with lethal doses of the hypervirulent Type I strain RH raising the question of relevance to hepatic infection with strains that are more commonly found in mice or humans. Using clinically isolated Type II strains, Toxoplasma cysts were found in the livers of infected Swiss-Webster mice as late as 33 weeks post-infection, indicating that the liver may be a reservoir for chronic infection (Autier et al, 2018). This is consistent with clinical reports of Toxoplasma -negative transplant recipients who have developed toxoplasmosis after receiving livers from sera positive donors (Assi et al, 2007; Galván-Ramírez et al, 2018).…”

Section: Host Metabolic Dysregulation In Toxoplasma Infectionmentioning

confidence: 99%

Disease Tolerance in Toxoplasma Infection

Melchor

Ewald

2019

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is a successful protozoan parasite that cycles between definitive felid hosts and a broad range of intermediate hosts, including rodents and humans. Within intermediate hosts, this obligate intracellular parasite invades the small intestine, inducing an inflammatory response. Toxoplasma infects infiltrating immune cells, using them to spread systemically and reach tissues amenable to chronic infection. An intact immune system is necessary to control life-long chronic infection. Chronic infection is characterized by formation of parasite cysts, which are necessary for survival through the gastrointestinal tract of the next host. Thus, Toxoplasma must evade sterilizing immunity, but still rely on the host's immune response for survival and transmission. To do this, Toxoplasma exploits a central cost-benefit tradeoff in immunity: the need to escalate inflammation for pathogen clearance vs. the need to limit inflammation-induced bystander damage. What are the consequences of sustained inflammation on host biology? Many studies have focused on aspects of the immune response that directly target Toxoplasma growth and survival, commonly referred to as “resistance mechanisms.” However, it is becoming clear that a parallel arm of the immune response has evolved to mitigate damage caused by the parasite directly (for example, egress-induced cell death) or bystander damage due to the inflammatory response (for example, reactive nitrogen species, degranulation). These so-called “disease tolerance” mechanisms promote tissue function and host survival without directly targeting the pathogen. Here we review changes to host metabolism, tissue structure, and immune function that point to disease tolerance mechanisms during Toxoplasma infection. We explore the impact tolerance programs have on the health of the host and parasite biology.

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The liver as an organ at risk forToxoplasmatransmission during transplantation: myth or reality?

Cited by 18 publications

References 24 publications

Imiquimod Targets Toxoplasmosis Through Modulating Host Toll-Like Receptor-MyD88 Signaling

Imiquimod Targets Toxoplasmosis Through Modulating Host Toll-Like Receptor-MyD88 Signaling

Toxoplasma gondii Monitoring in Liver Transplantation Patients: A Single Center Cross-Sectional Study in an Italian Hospital

Disease Tolerance in Toxoplasma Infection

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