T cell-derived interferon-γ is required for host defense to

Nishiyama, Saishi; Pradipta, Ariel; Su, Ji Guo; Sasai, Miwa; Yamamoto, Masahiro

doi:10.1016/j.parint.2019.102049

Cited by 17 publications

(13 citation statements)

References 32 publications

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“… 70 The latest evidence demonstrating the CD4 + , CD8 + , γδT cells, and NK cells as the main producers of IFNγ during toxoplasmosis was based on the use of a newly developed mouse line named as “GREVEN” an IFNγ reporter mouse having a fusion protein of Venus and NanoLuc to analyze IFNγ producing cells. 67 Likewise, the Lck-Cre/Ifngfl/fl mice were found highly susceptible to toxoplasmosis, further strengthening the role of T-cell-IFNγ in protection against toxoplasmosis. 67 At the site of infection, the maintenance of IFR8+ inflammatory DCs is essential provision of host resistance against intracellular T. gondii , whereas this requires the production of IFNγ by ILC1 and NK cells through T-bet involvement.…”

Section: Host Immune Responsementioning

confidence: 83%

“… 67 Likewise, the Lck-Cre/Ifngfl/fl mice were found highly susceptible to toxoplasmosis, further strengthening the role of T-cell-IFNγ in protection against toxoplasmosis. 67 At the site of infection, the maintenance of IFR8+ inflammatory DCs is essential provision of host resistance against intracellular T. gondii , whereas this requires the production of IFNγ by ILC1 and NK cells through T-bet involvement. 68 The extensive role of IFNγ was partly dependent on the release of TNFα by activated MΦs.…”

Section: Host Immune Responsementioning

confidence: 83%

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Immune response against toxoplasmosis—some recent updates RH:Toxoplasma gondiiimmune response

Sana

Rashid

et al. 2022

Int J Immunopathol Pharmacol

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Aims Cytokines, soluble mediators of immunity, are key factors of the innate and adaptive immune system. They are secreted from and interact with various types of immune cells to manipulate host body’s immune cell physiology for a counter-attack on the foreign body. A study was designed to explore the mechanism of Toxoplasma gondii ( T. gondii) resistance from host immune response. Methods and results The published data on aspect of host (murine and human) immune response against T. gondii was taken from Google scholar and PubMed. Most relevant literature was included in this study. The basic mechanism of immune response starts from the interactions of antigens with host immune cells to trigger the production of cytokines (pro-inflammatory and anti-inflammatory) which then act by forming a cytokinome (network of cytokine). Their secretory equilibrium is essential for endowing resistance to the host against infectious diseases, particularly toxoplasmosis. A narrow balance lying between Th1, Th2, and Th17 cytokines (as demonstrated until now) is essential for the development of resistance against T. gondii as well as for the survival of host. Excessive production of pro-inflammatory cytokines leads to tissue damage resulting in the production of anti-inflammatory cytokines which enhances the proliferation of Toxoplasma. Stress and other infectious diseases (human immunodeficiency virus (HIV)) that weaken the host immunity particularly the cellular component, make the host susceptible to toxoplasmosis especially in pregnant women. Conclusion The current review findings state that in vitro harvesting of IL12 from DCs, Np and MΦ upon exposure with T. gondii might be a source for therapeutic use in toxoplasmosis. Current review also suggests that therapeutic interventions leading to up-regulation/supplementation of SOCS-3, IL12, and IFNγ to the infected host could be a solution to sterile immunity against T. gondii infection. This would be of interest particularly in patients passing through immunosuppression owing to any reason like the ones receiving anti-cancer therapy, the ones undergoing immunosuppressive therapy for graft/transplantation, the ones suffering from immunodeficiency virus (HIV) or having AIDS. Another imortant suggestion is to launch the efforts for a vaccine based on GRA6Nt or other similar antigens of T. gondii as a probable tool to destroy tissue cysts.

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Section: Host Immune Responsementioning

confidence: 83%

Section: Host Immune Responsementioning

confidence: 83%

Immune response against toxoplasmosis—some recent updates RH:Toxoplasma gondiiimmune response

Sana

Rashid

et al. 2022

Int J Immunopathol Pharmacol

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“…This indicated that peptide 6027 promoted, rather than inhibited, the infection process in vivo, which in turn could be due to a potential interference in the immune response. As IFN-γ is the major cytokine known to confer protective immunity against T. gondii infection [ 26 ], we investigated the production of this cytokine in splenocyte cultures obtained from these experimentally infected mice. While ConA-stimulated splenocytes obtained from peptide 6027-treated mice, no matter whether they were infected or not, displayed a reduced IFN-γ production compared to the non-treated controls, no difference was noted in the two splenocyte populations from infected mice when they were stimulated with T. gondii extract.…”

Section: Discussionmentioning

confidence: 99%

Differential Affinity Chromatography Coupled to Mass Spectrometry: A Suitable Tool to Identify Common Binding Proteins of a Broad-Range Antimicrobial Peptide Derived from Leucinostatin

et al. 2022

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Leucinostatins are antimicrobial peptides with a broad range of activities against infectious agents as well as mammalian cells. The leucinostatin-derivative peptide ZHAWOC_6027 (peptide 6027) was tested in vitro and in vivo for activity against the intracellular apicomplexan parasite Toxoplasma gondii. While highly efficacious in vitro (EC50 = 2 nM), subcutaneous application of peptide 6027 (3 mg/kg/day for 5 days) in mice experimentally infected with T gondii oocysts exacerbated the infection, caused mild clinical signs and elevated cerebral parasite load. Peptide 6027 also impaired the proliferation and viability of mouse splenocytes, most notably LPS-stimulated B cells, in vitro. To identify common potential targets in Toxoplasma and murine splenocytes, we performed differential affinity chromatography (DAC) with cell-free extracts from T. gondii tachyzoites and mouse spleens using peptide 6027 or an ineffective analogue (peptide 21,358) coupled to N-hydroxy-succinimide sepharose, followed by mass spectrometry. Proteins specifically binding to peptide 6027 were identified in eluates from the peptide 6027 column but not in peptide 21,358 nor the mock column eluates. In T. gondii eluates, 269 proteins binding specifically to peptide 6027 were identified, while in eluates from mouse spleen extracts 645 proteins specifically binding to this peptide were detected. Both datasets contained proteins involved in mitochondrial energy metabolism and in protein processing and secretion. These results suggest that peptide 6027 interacts with common targets in eukaryotes involved in essential pathways. Since this methodology can be applied to various compounds as well as target cell lines or organs, DAC combined with mass spectrometry and proteomic analysis should be considered a smart and 3R-relevant way to identify drug targets in pathogens and hosts, thereby eliminating compounds with potential side effects before performing tedious and costly safety and efficacy assessments in animals or humans.

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“…IFN-γ is a characteristic cytokine of the Th1 profile, produced in response to intracellular infections, with fundamental importance in toxoplasmosis control ( 50 , 51 , 75 , 76 ). However, literature data vary as it has been reported that the serum IFN-γ concentrations of PW with GDM were similar ( 58 ), lower ( 70 ), and higher ( 77 ) than normoglycemic patients.…”

Section: Discussionmentioning

confidence: 99%

Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii

et al. 2022

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In order to evaluate and compare the specific immune response of pregnant women (PW) chronically infected with Toxoplasma gondii, with and without gestational diabetes mellitus (GDM), and the humoral response of their respective newborns (NB), the study was carried out on 81 PW (34 GDM and 47 controls) from whose medical records the results of the oral glucose tolerance test (OGTT) were obtained, and blood samples were collected at the third trimester of pregnancy; also, on 45 NBs (20 GDM and 25 controls) from whom umbilical cord blood samples were obtained. Humoral immunity was analyzed by measuring anti-T. gondii total IgG, IgG subclasses and IgG avidity. To evaluate cellular immunity, peripheral blood mononuclear cells (PBMC) from 32 PW (16 GDM and 16 controls) were cultured, supernatant cytokines were determined, and flow cytometry was performed to analyze the expression at lymphocytes of surface molecules, cytokines and transcription factors. All PW and NBs were positive for total IgG, and the prevalent subclass was IgG1. There was a negative correlation between the OGTT glycemia of PW and the levels of total IgG, IgG1 and IgG avidity. The IgG avidity of the GDM group was significantly lower than the control group. Patients from the GDM group had a higher number of T lymphocytes expressing markers of cell activation and exhaustion (CD28 and PD-1). In the presence of T. gondii soluble antigen (STAg) the amount of CD4+ T cells producing IFN-γ, IL-10 and IL-17 was significantly lower in the GDM group, while there was no difference between groups in the number of CD4+ CD25HighFOXP3+LAP+ functional Treg cells. Additionally, under STAg stimulus, the secretion of IL-17, IL-4, TNF and IL-2 cytokines at PBMCs culture supernatant was lower in the GDM group. In conclusion, there was a correlation between the increase in blood glucose and the decrease in levels of anti-T. gondii antibodies, associated with the decreased IgG avidity in patients who develop GDM. Also, the GDM group had decreased immune responses in Th1, Th2 and Th17 profiles, suggesting an association between GDM and the negative modulation of the humoral and cellular immune responses against T. gondii.

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T cell-derived interferon-γ is required for host defense to

Cited by 17 publications

References 32 publications

Immune response against toxoplasmosis—some recent updates RH:Toxoplasma gondiiimmune response

Immune response against toxoplasmosis—some recent updates RH:Toxoplasma gondiiimmune response

Differential Affinity Chromatography Coupled to Mass Spectrometry: A Suitable Tool to Identify Common Binding Proteins of a Broad-Range Antimicrobial Peptide Derived from Leucinostatin

Association of gestational diabetes mellitus and negative modulation of the specific humoral and cellular immune response against Toxoplasma gondii

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