The Neurotropic Parasite Toxoplasma gondii Induces Sustained Neuroinflammation with Microvascular Dysfunction in Infected Mice

Estato, Vanessa; Stipursky, Joice; Gomes, Filipa; Mergener, Tally C.; Frazão-Teixeira, Edwards; Allodi, Silvana; Tibiriçá, Eduardo; Barbosa, Helene Santos; Adesse, Daniel

doi:10.1016/j.ajpath.2018.07.007

Cited by 46 publications

(57 citation statements)

References 76 publications

(79 reference statements)

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“…Pro-inflammatory cytokines induced by T. gondii infection tend to exacerbate the disease itself or symptoms associated with the disease [ 25 , 48 , 49 ]. After infection with T. gondii ME49, pro-inflammatory cytokines appear most frequently in the brain.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

et al. 2020

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Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4+ and CD8+ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.

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Section: Discussionmentioning

confidence: 99%

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

et al. 2020

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“…A recent animal model study by Estato et al (25), showed that mice infected with T. gondii illustrated an exaggeration of leukocyte adhesion to the endothelial cells that caused endothelial dysfunction. Also, therapy with sulfadiazine improves endothelial dysfunction in acute toxoplasmosis through reduction of parasitic load and related endothelial inflammations (25).…”

Section: Discussionmentioning

confidence: 99%

Toxoplasmosis and Risk of Endothelial Dysfunction: Role of Oxidative Stress and Pro-Inflammatory Mediators

Al-Kuraishy

Al-Kuraishi

Al-Windy

et al. 2020

Arch Clin Infect Dis

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Background: Infection with Toxoplasma gondii (T. gondii) leads to activation of T-helper cells (Th-1 and Th-2) which are involved in the synthesis and release of different cytokines which may lead to endothelial dysfunction. Objectives: To evaluate the endothelial function in patients with acute toxoplasmosis. Methods: This case-control study involved 31 patients with toxoplasmosis aged 19 -47 years matched with 20 healthy subjects. Anti-T. gondii antibody (IgG, IgM, IgA) was determined by direct antigen-antibody reaction. Interleukin-6(IL-6), endothelin-1 (ET-1) and human malondialdehyde (MDA) serum levels were measured. Results: IgM, IgG and IgA levels were high in the infected patients compared with controls (P < 0.01). Furthermore, IL-6 serum level was high in the infected patients compared with controls (P < 0.01). In addition, ET-1 level was high in acute toxoplasmosis (7.29 ± 4.59 pg/mL) compared with controls (3.11 ± 1.69 pg/mL) (P < 0.01). In addition, MDA serum level was high (9.34 ± 4.17 nmol/mL) compared with controls (2.87 ± 1.13 nmol/mL), (P < 0.01). In acute toxoplasmosis IgM serum level was significantly correlated with IgG (r = 0.55, P = 0.001), IgA (r = 0.57, P = 0.0008), IL-6 (r = 0.45, P = 0.01), ET-1 (r = 0.51, P = 0.003) and MDA (r = 0.85, P = 0.0001). Conclusions: Acute toxoplasmosis is associated with significant oxidative stress and pro-inflammatory changes which contribute to development of endothelial dysfunction.

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“…anti-inflammatory cytokines and neurotrophic factors with potential neuroprotective properties, but excessively activated microglia could lead to neuronal apoptosis (Mahmoudvand et al, 2016;Estato et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of lncRNA-11496 in the Brain Contributes to Microglia Apoptosis via Regulation of Mef2c in Chronic T. gondii Infection Mice

Sun

Wang

et al. 2020

Front. Mol. Neurosci.

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Though it is well known that chronic infections of Toxoplasma gondii (T. gondii) can induce mental and behavioral disorders in the host, little is known about the role of long non-coding RNAs (lncRNAs) in this pathological process. In this study, we employed an advanced lncRNAs and mRNAs integration chip (Affymetrix HTA 2.0) to detect the expression of both lncRNAs and mRNAs in T. gondii Chinese 1 strain infected mouse brain. As a result, for the first time, the downregulation of lncRNA-11496 (NONMMUGO11496) was identified as the responsible factor for this pathological process. We showed that dysregulation of lncRNA-11496 affected proliferation, differentiation and apoptosis of mouse microglia. Furthermore, we proved that Mef2c (Myocyte-specific enhancer factor 2C), a member of the MEF2 subfamily, is the target gene of lncRNA-11496. In a more detailed study, we confirmed that lncRNA-11496 positively regulated the expression of Mef2c by binding to histone deacetylase 2 (HDAC2). Importantly, Mef2c itself could coordinate neuronal differentiation, survival, as well as synapse formation. Thus, our current study provides the first evidence in terms of the modulatory action of lncRNAs in chronic toxoplasmosis in T. gondii infected mouse brain, providing a solid scientific basis for using lncRNA-11496 as a therapeutic target to treat T. gondii induced neurological disorder.

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The Neurotropic Parasite Toxoplasma gondii Induces Sustained Neuroinflammation with Microvascular Dysfunction in Infected Mice

Cited by 46 publications

References 76 publications

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

Toxoplasmosis and Risk of Endothelial Dysfunction: Role of Oxidative Stress and Pro-Inflammatory Mediators

Downregulation of lncRNA-11496 in the Brain Contributes to Microglia Apoptosis via Regulation of Mef2c in Chronic T. gondii Infection Mice

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