Toxoplasma gondii Type I TR and ROP16 Synergistically Downregulate IL-12 to Inhibit Host Reactive Oxygen Species Production

Pathogens, Год журнала: 2025, Номер 14(2), С. 171 - 171

Опубликована: Фев. 8, 2025

Toxoplasma gondii is an obligate intracellular opportunistic protozoan parasite. T. invasion disturbs the balance between reactive oxygen species (ROS) production and antioxidant capacity in host, triggering oxidative stress response. Thioredoxin reductase (TR) of helps to escape ROS-induced damage whereas rhoptry protein 16 (ROP16) downregulates host innate immunity suppress excessive inflammation inhibit ROS production. However, whether TR ROP16 synergistically promote resistance remains unclear. Here, we used CRISPR/Cas9 technology successfully obtain a double gene knockout strain. The deletion weakened its growth ability vitro decreased virulence vivo. Moreover, resulted lower capacity, higher degree lipid oxidation, elevated levels parasite cells. Interestingly, genes increased IL-12 levels, which triggered cells produce more resist infection. These results show that play synergistic role, facilitating incurred by immune through different pathways.

Язык: Английский

Interferons and Toxoplasma shape PD-L1 regulation in retinal barrier cells: The critical role of proteases

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

The apicomplexan parasite Toxoplasma gondii establishes chronic infection in the central nervous system, including retina, causing ocular toxoplasmosis (OT). This persistence relies on a fine balance between inflammatory and immunomodulatory mechanisms, especially immune-privileged environment. We previously described immunologic interactions retinal cells, particularly roles of type I III interferons. In this study, we investigated regulatory dynamics PD-L1, receptor immune cells. first mechanisms PD-L1 regulation interferons an in vitro T. gondiiinfection model using mono- co-culture systems human microglia, astrocytes, Müller also assessed expression outer blood-retina barrier (oBRB) differentiated pigmented epithelial (RPE) Additionally, looked at cell activation, these mouse OT. Our findings reveal new for regulating glial activation RPE, Müller, astrocytes microglial Notably, most abundant cells showed highest baseline both mRNA protein levels, responded robustly to interferon stimulation. points more prominent immunoregulatory role retina than recognized. Furthermore, identified protease-dependent mechanism that reduces our vitrooBRB potentially contributing evasion inflammation during Finally, murine OT, demonstrated reached its peak day 7 post-infection neutralization plays crucial activation. orchestrates IFN dependent interaction downregulates oBRB by mechanism, infection. results can pave way fully elucidate networks offering potential targets therapeutic interventions OT other diseases.

Язык: Английский

Mutual regulations between Toxoplasma gondii and type I interferon

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 8, 2024

In the decades since discovery, Type I interferon (IFN-I) has been intensively studied for their antiviral activity. However, increasing evidences suggest that it may also play an important role in infection of Toxoplasma gondii , a model organism intracellular parasites. Recent studies demonstrated induction IFN-I by parasite depends on cell type, strain genotype, and mouse strain. can inhibit proliferation T. but few showed is beneficial to growth parasite. Meanwhile, secrete proteins impact pathway production downstream induced interferon-stimulated genes (ISGs) regulation, thereby escaping immune destruction host. This article reviews major findings progress production, function, regulation during infection, thoroughly understand innate mechanism which provides new target subsequent intervention treatment.

Язык: Английский