Inducible Nitric Oxide Synthase Is a Key Host Factor for<i>Toxoplasma</i>GRA15-Dependent Disruption of the Gamma Interferon-Induced Antiparasitic Human Response

Bando, Hironori; Lee, Youngae; Sakaguchi, Naoya; Pradipta, Ariel; Su, Ji Guo; Tanaka, S.; Yue, Cai; Liu, Jianfa; Shen, Jilong; Nishikawa, Yoshifumi; Sasai, Miwa; Yamamoto, Masahiro

doi:10.1128/mbio.01738-18

Cited by 37 publications

(41 citation statements)

References 62 publications

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“…Cytotoxicity to HFF cells induced by nullscript was measured as previously described ( Bando et al, 2018 ). The cell viability was monitored by measuring lactate dehydrogenase (LDH) leakage into the culture medium by using CytoTox96 Non-Radio Cytotoxicity Assay kit (Promega).…”

Section: Methodsmentioning

confidence: 99%

Nullscript inhibits Cryptosporidium and Toxoplasma growth

Murakoshi

Bando

Sugi

et al. 2020

International Journal for Parasitology: Drugs and Drug Resistan

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Cryptosporidium and Toxoplasma are parasites that have caused problems worldwide. Cryptosporidium causes severe watery diarrhoea and may be fatal in immunocompromised patients and in infants. Nitazoxanide is the only agent currently approved by the FDA, but its efficacy is limited. Toxoplasmosis is also a problem in the immunocompromised, as currently available treatment options have limited efficacy and patient tolerance can be poor. In the present investigation, we screened libraries of epigenetic compounds to identify those that inhibited C. parvum growth. Nullscript was identified as a compound with an inhibitory effect on C. parvum and T. gondii growth, and was less toxic to host cells. Nullscript was also able to significantly decrease oocyst excretion in C. parvum -infected SCID mice.

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Section: Methodsmentioning

confidence: 99%

Nullscript inhibits Cryptosporidium and Toxoplasma growth

Murakoshi

Bando

Sugi

et al. 2020

International Journal for Parasitology: Drugs and Drug Resistan

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“…With respect to human anti-parasitic effector mechanisms, IFN-γ-induced 2,3 indoleamine dioxygenase (IDO) degrades tryptophan and plays a role for parasite control by astrocytes (119). Interestingly, it has been demonstrated that the parasite aims to restrict anti-parasitic IDO levels in the host cell: the T. gondii effector molecule TgIST inhibits IDO1 mRNA expression and T. gondii GRA15-induced NO antagonizes IFN-γ-dependent IDO levels (120, 121). Importantly, the mechanisms leading to control and elimination of T. gondii in murine and human neurons are unknown.…”

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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“…In human cells, the effect of iNOS is different. It acts as a pro- Toxoplasma host factor through the GRA15-dependent virulence mechanism in the THP-1/Huh7 coculture mode (Bando et al., 2018). Upregulation of ROS and IDO generated by many cell types leads to inhibition of parasite replication.…”

Section: Resistance To Oxidative Stressmentioning

confidence: 99%

Strategies Developed by Toxoplasma gondii to Survive in the Host

Zhu

Pappoe

et al. 2019

Front. Microbiol.

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One of the most successful intracellular parasites, Toxoplasma gondii has developed several strategies to avoid destruction by the host. These include approaches such as rapid and efficient cell invasion to avoid phagocytic engulfment, negative regulation of the canonical CD40-CD40L-mediated autophagy pathway, impairment of the noncanonical IFN-γ-dependent autophagy pathway, and modulation of host cell survival and death to obtain lifelong parasite survival. Different virulent strains have even evolved different ways to cope with and evade destruction by the host. This review aims to illustrate every aspect of the game between the host and Toxoplasma during the process of infection. A better understanding of all aspects of the battle between Toxoplasma and its hosts will be useful for the development of better strategies and drugs to control the parasite.

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Inducible Nitric Oxide Synthase Is a Key Host Factor forToxoplasmaGRA15-Dependent Disruption of the Gamma Interferon-Induced Antiparasitic Human Response

Cited by 37 publications

References 62 publications

Nullscript inhibits Cryptosporidium and Toxoplasma growth

Nullscript inhibits Cryptosporidium and Toxoplasma growth

Advances and Challenges in Understanding Cerebral Toxoplasmosis

Strategies Developed by Toxoplasma gondii to Survive in the Host

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