Publication Details
Abstract
Trained immunity represents a paradigm shift in immunology, describing the capacity of innate immune cells to develop long-lasting functional reprogramming after primary stimulation, leading to enhanced or altered responses upon secondary challenge. Toxoplasma gondii, an obligate intracellular protozoan parasite, provides a unique model for studying trained immunity due to its ability to establish lifelong latent infection and induce sustained immune activation. This review explores current evidence on trained immunity and long-term immune modulation during T. gondii infection, with emphasis on innate immune memory, immunometabolic reprogramming, and epigenetic remodeling. During acute infection, T. gondii triggers strong innate responses mediated by monocytes, macrophages, dendritic cells, and natural killer cells, characterized by the production of interferon-γ and pro-inflammatory cytokines. Emerging data suggest that these early signals can imprint durable changes in innate immune cells and their progenitors, resulting in heightened responsiveness or immune tolerance during chronic infection. Metabolic shifts, including enhanced glycolysis and altered mitochondrial function, alongside epigenetic modifications such as histone methylation and acetylation, appear central to this process. While trained immunity may contribute to improved control of secondary infections, it may also promote chronic inflammation, immune exhaustion, or pathological immune responses, particularly in immunocompromised individuals. Understanding how T. gondii shapes long-term innate immune function has important implications for host susceptibility to co-infections, autoimmune conditions, and vaccine responsiveness. This review highlights recent advances, unresolved questions, and future perspectives on targeting trained immunity pathways as potential strategies for immunomodulation and host-directed therapies in toxoplasmosis and related infectious diseases.