Dissecting NK-neuronal interaction during Toxoplasma gondii infection

• Applicants: Professorin Dr. Ildikò Rita Dunay; Professor Dr. Christoph Siegfried Niki Klose
• Subject Area: Immunology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568537669

Toxoplasma gondii (T. gondii), a ubiquitous intracellular parasite with a profound ability to infect virtually all warm-blooded animals, is responsible for a significant public health concern. In humans, infection can lead to toxoplasmosis, which, while often asymptomatic in healthy individuals, poses severe risks to immunocompromised patients and pregnant women. Our research has demonstrated that group 1 innate lymphoid cells, which include conventional NK cells and ILC1, and which both produce IFN- as a main effector cytokine, contribute to the resistance against T. gondii infection. Furthermore, some published evidence suggests that NK cells could adopt an ILC1-like phenotype during T. gondii infection. However, whether these phenotypic alterations reflect NK cell plasticity and how this mechanism impacts protective immunity against the parasite remains unclear. Our objective is to shed light on this elusive aspect. Moreover, emerging evidence suggests T. gondii's potential triggering of various neurological disorders, including schizophrenia and other psychiatric conditions, underscoring the critical need to understand the parasite's interaction with the nervous system. The central (CNS) and enteric nervous systems (ENS) are intricate networks that regulate numerous vital functions, from cognition and sensory processing in the CNS to gastrointestinal motility and secretion in the ENS. T. gondii's ability to invade and persist in these neural environments suggests significant adaptations by both the parasite and host neurons. Mounting evidence argues for a close interaction of the immune system and the nervous system. In the context of T. gondii infection, IFN- mediates protective immunity against the parasite. In addition, this cytokine has the ability to influence neuronal functions directly by binding to the IFN- receptor expressed by neurons. Our proposal aims to uncover the interaction between T. gondii, innate lymphoid cells, and the nervous system. In Aim 1, we delve into how the plasticity of NK and ILC1 fate decisions affect the resistance against T. gondii infection. Aim 2 focuses on monitoring the neuronal adaptations to T. gondii infection by examining the entire transcriptome of the ENS and CNS using sort-purification of fluorescently-tagged neuronal nuclei. The role of IFN- receptor in neurons during T. gondii infection will also be elucidated. In Aim 3, we will explore how T. gondii infection and NK cells influence neuronal functions in the peripheral and central nervous system. Uncovering the molecular interactions between T. gondii's infections, the innate immune response and its impact on neuronal function has the potential to lead to the development of targeted therapies and interventions.

• DFG Programme: Research Grants