Inducible Nitric Oxide Synthase Is a Key Host Factor for Toxoplasma GRA15-Dependent Disruption of the Gamma Interferon-Induced Antiparasitic Human Response (Yamamoto Lab, in mBio)

Toxoplasma, an important intracellular parasite of humans and animals, causes life-threatening toxoplasmosis in immunocompromised individuals. Interferon-γ (IFN-γ) is produced in the host to inhibit the proliferation of this parasite and eventually cause its death. Unlike mouse disease models, which involve well-characterized virulence strategies that are used by Toxoplasma to suppress IFN-γ-dependent immunity, the strategies used by Toxoplasma in humans remain unclear. Here, we show that GRA15, a Toxoplasma effector protein, suppresses the IFN-γ-induced indole-2,3-dioxygenase 1-dependent anti-parasite immune response in human cells. Because NLRP3-dependent production of IL-1β and nitric oxide (NO) in Toxoplasma-infected human cells is involved in the GRA15-dependent virulence mechanism, blocking NO production or IL-1β in the host could represent a novel therapeutic approach for treating human toxoplasmosis.

This article was published online in mBio on Oct 9, 2018

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

Hironori Bando, Youngae Lee, Naoya Sakaguchi, Ariel Pradipta, Ji Su Ma, Shun Tanaka, Yihong Cai, Jianfa Liu, Jilong Shen, Yoshifumi Nishikawa, Miwa Sasai, and Masahiro Yamamoto