Toxoplasma and Dendritic Cells: An Intimate Relationship That Deserves Further Scrutiny

Poncet, Anaïs; Blanchard, Nicolas; Marion, Sabrina

doi:10.1016/j.pt.2019.08.001

Cited by 16 publications

(21 citation statements)

References 114 publications

(149 reference statements)

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“…host-species dependent (reviewed in Hakimi et al, 2017;Lima and Lodoen, 2019;Poncet et al, 2019;Zhu et al, 2019;Wong et al, 2020).…”

Section: Srs52a Mic1 (T Sz) Mic2-m2ap (T B Sz) Got1 Family Proteinmentioning

confidence: 99%

“…GRA18 (conserved across the Toxoplasma lineages) induces b-catenindependent genes associated with anti-inflammatory responses, including CCL17 and CCL22 chemokines in murine infected macrophages (He et al, 2018). Toxoplasma inhibitor of STAT1dependent transcription (TgIST) (type I, II), which represses STAT1-dependent promoters (Gay et al, 2016;Olias et al, 2016) could be the effector responsible for the dysregulation of MHC II molecule expression in infected host cells (Poncet et al, 2019). ROP16 (type I, III) phosphorylates STAT3 and STA6, mainly leading to a decrease in IL-12 and Th1 response (Saeij et al, 2007;Yamamoto et al, 2009;Ong et al, 2010).…”

Section: Srs52a Mic1 (T Sz) Mic2-m2ap (T B Sz) Got1 Family Proteinmentioning

confidence: 99%

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Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Mévélec

Lakhrif

Dimier‐Poisson

2020

Front. Cell. Infect. Microbiol.

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Toxoplasmosis is a parasitic disease affecting human, livestock and cat. Prophylactic strategies would be ideal to prevent infection. In a One Health vaccination approach, the objectives would be the prevention of congenital disease in both women and livestock, prevention/reduction of T. gondii tissue cysts in food-producing animals; and oocyst shedding in cats. Over the last few years, an explosion of strategies for vaccine development, especially due to the development of genetic-engineering technologies has emerged. The field of vaccinology has been exploring safer vaccines by the generation of recombinant immunogenic proteins, naked DNA vaccines, and viral/bacterial recombinants vectors. These strategies based on single- or few antigens, are less efficacious than recombinant live-attenuated, mostly tachyzoite T. gondii vaccine candidates. Reflections on the development of an anti-Toxoplasma vaccine must focus not only on the appropriate route of administration, capable of inducing efficient immune response, but also on the choice of the antigen (s) of interest and the associated delivery systems. To answer these questions, the choice of the animal model is essential. If mice helped in understanding the protection mechanisms, the data obtained cannot be directly transposed to humans, livestock and cats. Moreover, effectiveness vaccines should elicit strong and protective humoral and cellular immune responses at both local and systemic levels against the different stages of the parasite. Finally, challenge protocols should use the oral route, major natural route of infection, either by feeding tissue cysts or oocysts from different T. gondii strains. Effective Toxoplasma vaccines depend on our understanding of the (1) protective host immune response during T. gondii invasion and infection in the different hosts, (2) manipulation and modulation of host immune response to ensure survival of the parasites able to evade and subvert host immunity, (3) molecular mechanisms that define specific stage development. This review presents an overview of the key limitations for the development of an effective vaccine and highlights the contributions made by recent studies on the mechanisms behind stage switching to offer interesting perspectives for vaccine development.

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“…host-species dependent (reviewed in Hakimi et al, 2017;Lima and Lodoen, 2019;Poncet et al, 2019;Zhu et al, 2019;Wong et al, 2020).…”

Section: Srs52a Mic1 (T Sz) Mic2-m2ap (T B Sz) Got1 Family Proteinmentioning

confidence: 99%

Section: Srs52a Mic1 (T Sz) Mic2-m2ap (T B Sz) Got1 Family Proteinmentioning

confidence: 99%

Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Mévélec

Lakhrif

Dimier‐Poisson

2020

Front. Cell. Infect. Microbiol.

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“…Toxoplasmosis manifests as acute and chronic forms (AT and CT, respectively). In immunocompetent hosts, AT is caused by the presence of replicating tachyzoïtes, which convert in the brain and the skeletal muscles into persistent bradyzoïte cysts [(4, 5), reviewed in Wohlfert et al (6), Poncet et al (7)].…”

Section: Introductionmentioning

confidence: 99%

“…Following infection with T. gondii, TLRs expressed on innate immune cells detect the parasite (45). Murine TLR-11 and 12 of DCs, recognize Profilin, a Toxoplasma Pathogen-associated molecular pattern (PAMP) [ (46)(47)(48), reviewed in Poncet et al (7)], to primarily signal through the adaptor protein MyD88 (49), leading to the activation of several signaling pathways including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK). This subsequently mounts the protective immune response through the production of interleukin-12 (IL-12), Interferon-gamma (IFN-γ), among others (47,50).…”

Section: Introductionmentioning

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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“…The activation of CD8 + T cells is essential for inhibition of T. gondii infection [16]. Dendritic cells and macrophages are important antigen-presenting cells for T cells, which play important roles in antiinfection [17,18]. The communication between these immune cells is particularly important.…”

Section: Introductionmentioning

confidence: 99%

Anti-Infection Roles of mir155-5p Packaged in Exosomes Secreted by Dendritic Cells Infected with Toxoplasma Gondii

Jiang¹,

Wu²,

Xu³

et al. 2021

Preprint

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Background: Toxoplasma gondii is a zoonotic intracellular protozoon that is estimated to infect about 30% of the world’s population, resulting in toxoplasmosis in immuno-compromised patients and adverse outcomes in the primary infection during pregnancy. Exosomes are tubular vesicles secreted by cells, and they function in intercellular communication. It has been reported that the exosomes secreted by T. gondii-infected immune cells transmit infection signals to the uninfected cells. However, the mechanism and effect of the exosome transmission are still vague. We therefore investigated the function of the exosomes transmitted from DC2.4 cells infected with T. gondii RH strain (Tg-DC-Exo) to the uninfected cells, as well as their roles in anti-infection. Methods: We conducted exosome isolation and identification with ultracentrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blotting. Recipient cells taken up exosomes by PKH67 assay. The signal transmission and the abundance of mir155-5p were determined using transwell assay and qRT-PCR. For the immune responses, cytokines was evaluated. T. gondii B1 gene was determined to evaluate tachyzoites proliferation.Results: We observed that Toxoplasma infection up-regulated mir155-5p expression in DC2.4 cells secreted exosomes, and those exosomes can be ingested by murine macrophage RAW264.7 cells. Tg-DC-Exo and mir155-5p stimulating host proinflammatory immune responses such as proinflammatory cytokine (IL6,iNOS and TNF-α) production increased and NF-κB signal pathway activation by down regulating SOCS1, leading to inhibit T. gondii tachyzoite proliferation in RAW264.7 cells. Conclusion: Our findings provide a novel mechanism for how infected cells transmit infection signals to the uninfected cells through exosome secretion after T. gondii infection, followed by inflammatory responses and anti-infection reactions, which may help us develop a new intervention strategy for toxoplasmosis prevention, especially in immuno-compromised patients.

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Toxoplasma and Dendritic Cells: An Intimate Relationship That Deserves Further Scrutiny

Cited by 16 publications

References 114 publications

Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

Key Limitations and New Insights Into the Toxoplasma gondii Parasite Stage Switching for Future Vaccine Development in Human, Livestock, and Cats

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

Anti-Infection Roles of mir155-5p Packaged in Exosomes Secreted by Dendritic Cells Infected with Toxoplasma Gondii

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