Incidence of toxoplasma retinochoroiditis in patients with ankylosing spondylitis after using TNF-α blockers

Rodrigues, Kelly Fernandes de Paula; Arantes, Tiago Eugênio Faria e; Muccioli, Cristina; Neto, João Lins de Andrade; Pinheiro, Marcelo M.

doi:10.1016/j.parint.2013.02.003

Cited by 17 publications

(14 citation statements)

References 26 publications

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“…One might also expect that severe toxoplasmosis may manifest upon iatrogenic immunosuppression by T cell-ablating antibodies and anti-cytokine/cytokine receptor therapy. However, although anti-TNF therapy is becoming common, only very few cases of severe toxoplasmosis, reactivated TE or OT have been reported in patients undergoing anti-TNF therapy (145–147). In contrast, mice treated with anti-TNF show an impaired parasite control (148).…”

Section: Chronic Infection In the Brain Parenchymamentioning

confidence: 99%

Advances and Challenges in Understanding Cerebral Toxoplasmosis

2019

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Toxoplasma gondii is a widespread parasitic pathogen that infects over one third of the global human population. The parasite invades and chronically persists in the central nervous system (CNS) of the infected host. Parasite spread and persistence is intimately linked to an ensuing immune response, which does not only limit parasite-induced damage but also may facilitate dissemination and induce parasite-associated immunopathology. Here, we discuss various aspects of toxoplasmosis where knowledge is scarce or controversial and, the recent advances in the understanding of the delicate interplay of T. gondii with the immune system in experimental and clinical settings. This includes mechanisms for parasite passage from the circulation into the brain parenchyma across the blood-brain barrier during primary acute infection. Later, as chronic latent infection sets in with control of the parasite in the brain parenchyma, the roles of the inflammatory response and of immune cell responses in this phase of the disease are discussed. Additionally, the function of brain resident cell populations is delineated, i.e., how neurons, astrocytes and microglia serve both as target cells for the parasite but also actively contribute to the immune response. As the infection can reactivate in the CNS of immune-compromised individuals, we bring up the immunopathogenesis of reactivated toxoplasmosis, including the special case of congenital CNS manifestations. The relevance, advantages and limitations of rodent infection models for the understanding of human cerebral toxoplasmosis are discussed. Finally, this review pinpoints questions that may represent challenges to experimental and clinical science with respect to improved diagnostics, pharmacological treatments and immunotherapies.

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Section: Chronic Infection In the Brain Parenchymamentioning

confidence: 99%

Advances and Challenges in Understanding Cerebral Toxoplasmosis

2019

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“…It has been reported that the use of anti-TNF antibodies against mice or macrophages can induce the transformation of bradyzoites to tachyzoites and tachyzoites proliferate ( Rodrigues et al, 2013 ). Therefore, we detected relative expression levels of BAG1 and SAG1 mRNA in mice brain.…”

Section: Discussionmentioning

confidence: 99%

Risk Assessment of Etanercept in Mice Chronically Infected With Toxoplasma gondii

Yang

Wang

et al. 2018

Front. Microbiol.

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Toxoplasma gondii (T. gondii) is a zoonotic parasite that severely harms the health of the host. The cysts of T. gondii can reactivate from bradyzoites to tachyzoites, if the individual develops low or defective immunity, causing lethal toxoplasmosis. The host resists T. gondii infection by mediating Th1-type cellular immunity to generate pro-inflammatory cytokines. Tumor necrosis factor (TNF) is an important pro-inflammatory cytokine, which can induce lysosomal fusion of parasitophorous vacuole (PV) to kill parasites. Etanercept is a soluble TNF receptor fusion protein, which is widely used clinically to cure autoimmune diseases. The effects and specific molecular mechanisms of etanercept treatment on patients co-infected with autoimmune diseases and chronic toxoplasmosis are rarely reported. In our study, a mouse model of chronic infection with T. gondii and murine macrophages RAW264.7 cells infected with T. gondii were employed to investigate the impact of etanercept on the status of chronic infection. The cytokines levels and a series of phenotypic experiments in vivo and in vitro were measured. In the present study, the expression levels of TNF, IL-1β, and IL-6 were decreased and the brain cysts number was increased in mice chronically infected with T. gondii after being treated with etanercept. In vivo experiments confirmed that etanercept caused a decrease in the immune levels of the mice and activated the brain cysts, which would lead to conversion from chronic infection to acute infection, causing severe clinical and pathological symptoms. Murine macrophages RAW264.7 cells were pretreated with etanercept, and then infected with T. gondii. In vitro experiments, the expression levels of cytokines were decreased, indicating that etanercept could also reduce the cells’ immunity and promote the transformation of bradyzoites to tachyzoites, but did not affect the intracellular replication of tachyzoites. In summary, etanercept treatment could activate the conversion of bradyzoites to tachyzoites through reducing host immunity in vivo and in vitro. The results obtained from this study suggest that the use of etanercept in patients co-infected with autoimmune diseases and chronic toxoplasmosis may lead to the risk of activation of chronic infection, resulting in severe acute toxoplasmosis.

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“…Macrophages mediate immune response through the secretion of some important immune regulatory factors such as TNF-α, IL-1β, TGF-1β, and IL-10 (Rodrigues et al, 2013; Waters et al, 2013; Berghaus et al, 2014). Barbara reported that T. gondii actively interfered with activation of the NF-κB pathway in macrophages, which led to disturbances in IL-12 and TNF-α production, enabling parasite survival within the host (Butcher et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Effects of Recombinant Toxoplasma gondii Citrate Synthase I on the Cellular Functions of Murine Macrophages In vitro

Liu

Sun

et al. 2017

Front. Microbiol.

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Toxoplasmosis, which is one of the most widespread zoonoses worldwide, has a high incidence and infection can result in severe disease in humans and livestock. Citrate synthase (CS) is a component of nearly all living cells that plays a vital role in the citric acid cycle, which is the central metabolic pathway of aerobic organisms. In the present study, the citrate synthase I gene of Toxoplasma gondii (T. gondii) (TgCSI) was cloned and characterized. The TgCSI gene had an open reading frame of 1665 bp nucleotides encoding a 555 amino acid protein with a molecular weight of 60 kDa. Using western blotting assay, the recombinant protein was successfully recognized by the sera of rats experimentally infected with T. gondii, while the native protein in the T. gondii tachyzoites was detected in sera from rats immunized with the recombinant protein of TgCSI. Binding of the protein to murine macrophages was confirmed by immuno fluorescence assay. Following incubation of macrophages with rTgCSI, the rTgCSI protein was found to have a dual function, with low concentrations (5–10 μg/mL) enhancing phagocytosis and high levels (80 μg/mL) inhibiting phagocytosis. Investigation of murine macrophage apoptosis illustrated that 5 μg/mL rTgCSI protein can significantly induce early apoptosis and late stage apoptosis (*p < 0.05), while 10 μg/mL rTgCSI protein significantly induced early apoptosis, but had no effect on late stage of apoptosis (**p < 0.01), and 80 μg/mL rTgCSI protein inhibited late stage apoptosis of macrophages (*p < 0.05). Cytokine detection revealed that the secretion of interleukin-10, interleukin-1β, transforming growth factor-β1 and tumor necrosis factor-α of macrophages increased after the cells were incubated with all concentration of rTgCSI, with the exception that 5 μg/mL rTgCSI had no effect on the secretion of interleukin-10 and interleukin-1β. However, secretion of NO and cell proliferation of the macrophages were substantially reduced. Taken together, these results suggested that TgCSI can affect the immune functions of murine macrophages by binding to the cells in vitro.

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Incidence of toxoplasma retinochoroiditis in patients with ankylosing spondylitis after using TNF-α blockers

Cited by 17 publications

References 26 publications

Advances and Challenges in Understanding Cerebral Toxoplasmosis

Advances and Challenges in Understanding Cerebral Toxoplasmosis

Risk Assessment of Etanercept in Mice Chronically Infected With Toxoplasma gondii

Effects of Recombinant Toxoplasma gondii Citrate Synthase I on the Cellular Functions of Murine Macrophages In vitro

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