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Toxoplasma Effector GRA15-Dependent Suppression of IFN-?-Induced Antiparasitic Response in Human Neurons.


ABSTRACT: Toxoplasma gondii is an important human and animal pathogen that causes life-threatening toxoplasmosis. The host immune system produces interferon-? (IFN-?) to inhibit T. gondii proliferation. IFN-?-inducible indole-2,3-dioxygenase 1 (IDO1), which mediates tryptophan degradation, has a major role in anti-T. gondii immune responses in various human cells. In response to the host's immune system, T. gondii secretes many virulence molecules into the host cells to suppress IFN-?-dependent antiparasitic immune responses. The GRA15-induced proparasitic mechanism for suppressing IDO1-dependent immune responses has previously been tested only in human hepatocyte and monocyte co-cultures. Thus, whether human cells other than hepatocytes contain this virulence mechanism remains unclear. Here, we show that the GRA15-dependent virulence mechanism for suppressing the IDO1-dependent anti-T. gondii response operates in human neuronal cell lines and primary human neurons. Analysis of various human cell lines revealed that IL-1?-induced iNOS-dependent reduction of IDO1 mRNA expression occurred in brain cell lines (A172; glioblastoma, IMR-32; neuroblastoma, and T98G; glioblastoma) and liver cell lines (Huh7 and HepG2), but not in other cell lines. Moreover, co-culturing type II T. gondii-infected THP-1 human monocytes with the brain cell lines inhibited the IDO1-mediated anti-T. gondii response in a GRA15-dependent manner. These data suggest that a GRA15-dependent virulence mechanism antagonizes the IDO1-dependent host immune response in human brain cells.

SUBMITTER: Bando H 

PROVIDER: S-EPMC6504700 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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<i>Toxoplasma</i> Effector GRA15-Dependent Suppression of IFN-γ-Induced Antiparasitic Response in Human Neurons.

Bando Hironori H   Lee Youngae Y   Sakaguchi Naoya N   Pradipta Ariel A   Sakamoto Ryoma R   Tanaka Shun S   Ma Ji Su JS   Sasai Miwa M   Yamamoto Masahiro M  

Frontiers in cellular and infection microbiology 20190501


<i>Toxoplasma gondii</i> is an important human and animal pathogen that causes life-threatening toxoplasmosis. The host immune system produces interferon-γ (IFN-γ) to inhibit <i>T. gondii</i> proliferation. IFN-γ-inducible indole-2,3-dioxygenase 1 (IDO1), which mediates tryptophan degradation, has a major role in anti-<i>T. gondii</i> immune responses in various human cells. In response to the host's immune system, <i>T. gondii</i> secretes many virulence molecules into the host cells to suppres  ...[more]

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