A systematic review on the role of GRA proteins of Toxoplasma gondii in host immunization

Rezaei, Fatemeh; Sharif, M.; Sarvi, Shahabeddin; Hejazi‬, ‪Seyed Hossein; Aghayan, Sargis A.; Pagheh, Abdol Sattar; Dodangeh, Samira; Daryani, Ahmad

doi:10.1016/j.mimet.2019.105696

Cited by 26 publications

(21 citation statements)

References 38 publications

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“…T. gondii releases excretory/secretory proteins (ESP) into the culture medium of cell culture tachyzoites, including components that specifically bind to the serum antibodies of previously infected patients and components with protease activity ( Ahn et al., 2001 ; Saadatnia et al., 2012 ). Like TLA components, they are the predominant candidate vaccines to activate host immunity and play an anti-tumor role ( Rezaei et al., 2019 ). T. gondii ESP can induce apoptosis of human K562 erythroleukemic cells, breast cancer MCF-7 cells, prostate cancer DU145 cells, and other cells, and inhibit the growth of B16F10 melanoma, Lewis lung carcinoma, and prostate cancer ( Wu et al., 2012 ).…”

Section: T Gondii Molecules Participate In Anti-tumor Immuni...mentioning

confidence: 99%

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

Chen

Liao

Peng

2022

Front. Cell. Infect. Microbiol.

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Tumor cells can successfully escape the host immune attack by inducing the production of immunosuppressive cells and molecules, leading to an ineffective tumor treatment and poor prognosis. Although immunotherapies have improved the survival rate of cancer patients in recent years, more effective drugs and therapies still need to be developed. As an intracellular parasite, Toxoplasma gondii can trigger a strong Th1 immune response in host cells, including upregulating the expression of interleukin-12 (IL-12) and interferon-γ (IFN-γ). Non-replicating uracil auxotrophic strains of T. gondii were used to safely reverse the immunosuppression manipulated by the tumor microenvironment. In addition to the whole lysate antigens, T. gondii-secreted effectors, including Toxoplasma profilin, rhoptry proteins (ROPs), and dense granule antigens (GRAs), are involved in arousing the host’s antigen presentation system to suppress tumors. When T. gondii infection relieves immunosuppression, tumor-related myeloid cells, including macrophages and dendritic cells (DCs), are transformed into immunostimulatory phenotypes, showing a powerful Th1 immune response mediated by CD8+ T cells. Afterwards, they target and kill the tumor cells, and ultimately reduce the size and weight of tumor tissues. This article reviews the latest applications of T. gondii in tumor therapy, including the activation of cellular immunity and the related signal pathways, which will help us understand why T. gondii infection can restrain tumor growth.

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Section: T Gondii Molecules Participate In Anti-tumor Immuni...mentioning

confidence: 99%

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

Chen

Liao

Peng

2022

Front. Cell. Infect. Microbiol.

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“…Meanwhile, dense granule proteins GRAs abundantly secreted by both T. gondii tachyzoites and bradyzoites exhibit strong immunogenicity. These immunogenic antigens could be detected throughout the T. gondii infection process at both acute and chronic phases [20,30]. Hence, the prolonged expression of GRAs as well as their immunogenicity make them ideal diagnostic antigens [44].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of recombinant nanoluciferase fused <i>Toxoplasma gondii</i> antigens in Luciferase-linked Antibody Capture Assay (LACA) for <i>Toxoplasma</i> infection in pigs

et al. 2022

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Toxoplasmosis is a widespread protozoan zoonosis. Since ingesting undercooked meat harboring Toxoplasma gondii cyst is considered one of the major transmission routes to humans, the screening of T. gondii in meat-producing animals can reduce the risk of food-borne toxoplasmosis in humans. Among serological diagnostic methods, Luciferase-linked Antibody Capture Assay (LACA) has been found to be a promising platform with high sensitivity and specificity. In this study, we aimed to evaluate recombinant nanoluciferase fused-T. gondii antigens (rNluc-GRA6, rNluc-GRA7, rNluc-GRA8 and rNluc-BAG1) for their potential use in LACA for pigs. As a result, the sensitivity of GRA6-, GRA7-, GRA8-and BAG1-LACA were 70.0%, 80.0%, 80.0% and 30.0% with specificity 87.0%, 81.5%, 74.1% and 50.0%, respectively. The cocktail LACA using a mixture of rNluc-GRA6, rNluc-GRA7 and rNluc-GRA8 indicated higher sensitivity (90.0%) and a similar specificity (96.3%) in comparison with the commercial ELISA kit.Compared to the Dye-Test as a reference test, cocktail LACA showed strong agreement (kappa value = 0.811) when we assessed pig sera collected at the slaughterhouse. In addition, we also successfully established the rapid LACA format for the detection of Toxoplasma infection in pigs (called Rapid-LACA) in which the test could be performed within 30 min. In Rapid-LACA, the protein A pre-coated/blocked plates could be preserved at -30℃, 4℃ or room temperature conditions for at least two months without compromising on the quality of assay.

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“…Secreted GRA15 has been identified as a major factor that contributes to the strain-specific differences in NFκB activation ( 15 ). Meanwhile, GRA7 produces a strong antibody response in the acute phase of infection ( 22 ) and has been tested as a candidate for vaccine development ( 23 ). Recent studies have revealed that GRA7 associates with ROP2 and ROP4, and functions in concert with ROP18 protein complexes that resist IFN-γ-activated host immune-related GTPase ( 24 – 26 ).…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Dense Granule Proteins 7, 14, and 15 Are Involved in Modification and Control of the Immune Response Mediated via NF-κB Pathway

et al. 2020

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Toxoplasma gondii infects almost all warm-blooded animals, including humans, leading to both cellular and humoral immune responses in the host. The virulence of T. gondii is strain specific and is defined by secreted effector proteins that disturb host immunity. Here, we focus on nuclear factor-kappa B (NFκB) signaling, which regulates the induction of T-helper type 1 immunity. A luciferase assay for screening effector proteins, including ROPs and GRAs that have biological activity against an NFκB-dependent reporter plasmid, found that overexpression of GRA7, 14, and 15 of a type II strain resulted in a strong activity. Thus, our study was aimed at understanding the involvement of NFκB in the pathogenesis of toxoplasmosis through a comparative analysis of these three molecules. We found that GRA7 and GRA14 were partially involved in the activation of NFκB, whereas GRA15 was essential for NFκB activation. The deletion of GRA7, GRA14, and GRA15 in the type II Prugniaud (Pru) strain resulted in a defect in the nuclear translocation of RelA. Cells infected with the Pru gra15 parasite showed reduced phosphorylation of inhibitor-κBα. GRA7, GRA14, and GRA15 deficiency decreased the levels of interleukin-6 in RAW246.7 cells, and RNA-seq analysis revealed that GRA7, GRA14, and GRA15 deficiency predominantly resulted in downregulation of gene expression mediated by NFκB. The virulence of all mutant strains increased, but Pru gra14 only showed a slight increase in virulence. However, the intra-footpad injection of the highly-virulent type I RH gra14 parasites in mice resulted in increased virulence. This study shows that GRA7, 14, and 15-induced host immunity via NFκB limits parasite expansion.

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A systematic review on the role of GRA proteins of Toxoplasma gondii in host immunization

Cited by 26 publications

References 38 publications

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

Diagnostic value of recombinant nanoluciferase fused <i>Toxoplasma gondii</i> antigens in Luciferase-linked Antibody Capture Assay (LACA) for <i>Toxoplasma</i> infection in pigs

Toxoplasma gondii Dense Granule Proteins 7, 14, and 15 Are Involved in Modification and Control of the Immune Response Mediated via NF-κB Pathway

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