Toxoplasma gondii can infect homoeothermic animals including humans and cause lethal toxoplasmosis in immunocompromised individuals. When hosts are infected with T. gondii, the cells induce immune responses against T. gondii. The pathogen infection is recognized by immune sensors that directly detect T. gondii structural components, leading to production of pro-inflammatory cytokines and chemokines. Antigen-presenting cells such as macrophages and dendritic cells strongly activate T cells and induce development of Th1 cells and antigen-specific killer CD8 T cells. These T cells and Group 1 innate lymphoid cells are main producers of IFN-γ, which robustly stimulates cell-autonomous immunity in cells infected with T. gondii. IFN-γ-inducible effectors such as IFN-inducible GTPases, inducible nitric oxide synthase and indoleamine-2,3-dioxygenase differentially play important roles in suppression of T. gondii growth and its direct killing in anti-T. gondii cell-autonomous immune responses. In this review, we will describe our current knowledge of innate, adaptive and IFN-γ-mediated cell-autonomous immunity against T. gondii infection.

Irgb6 has a role in the cell-autonomous response against T. gondii and involves ubiquitination and breakdown of vacuoles via binding of a specific phospholipid on the parasitophorous vacuole membrane.

Takotsubo cardiomyopathy is a reversible cardiomyopathy with a unique morphological feature of the left ventricle characterized by an apical ballooning appearance known for approximately known 25 years. Catecholamine drive plays an essential role in the pathogenesis and pathophysiology of Takotsubo cardiomyopathy; hence, it is also called stress cardiomyopathy. Physical stress could also have an impact and leads to a greater variety of characteristics in Takotsubo cardiomyopathy. Supportive and symptomatic medication remains the mainstay therapy with priority to improving the function of the left ventricle for several days and full recovery in 3-4 weeks. Due to its similarity with myocardial infarction, Takotsubo cardiomyopathy requires careful diagnosis and management for the best possible outcome.

Toxoplasma gondii is an important human and animal pathogen that causes life-threatening toxoplasmosis. Interferon-γ (IFN-γ) is critical for anti-T. gondii cell-autonomous immunity in both humans and mice. To proliferate efficiently within the hosts, virulent strains of T. gondii can suppress IFN-γ-dependent immunity. During parasite infection, it is well-characterized that various virulence effectors are secreted to transcriptionally or post-translationally target IFN-γ-inducible GTPases, which are essential for anti-parasite responses in mice. However, the role of IFN-γ-inducible GTPases in anti-T. gondii responses in human cells is controversial since they are non-functional or absent in humans. Instead, IFN-γ-induced tryptophan degradation by indole-2,3-dioxygenase (IDO) is important for the anti-T. gondii human response. To date, the T. gondii virulent mechanism targeting IDO in human cells remains elusive. Here we show that although humans possess two IDO isozymes, IDO1 and IDO2, human cells of various origins require IDO1 but not IDO2 for IFN-γ-induced cell-autonomous immunity to T. gondii. T. gondii secretes an effector TgIST to inhibit IDO1 mRNA expression. Taken together, the data suggests that T. gondii possesses virulence programs operated by TgIST to antagonize IFN-γ-induced IDO1-mediated anti-parasite cell-autonomous immunity in human cells.

Toxoplasma, an important intracellular parasite of humans and animals, causes life-threatening toxoplasmosis in immunocompromised individuals. Gamma interferon (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 antiparasite 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 or IL-1β production in the host could represent a novel therapeutic approach for treating human toxoplasmosis.