Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases

Abstract

Toxoplasma gondii (T. gondii) is a prevalent protozoan parasite of medical and veterinary significance. It is the etiologic agent of toxoplasmosis, a neglected disease in which incidence and symptoms differ between patients and regions. In immunocompetent patients, toxoplasmosis manifests as acute and chronic forms. Acute toxoplasmosis presents as mild or asymptomatic disease that evolves, under the host immune response, into a persistent chronic disease in healthy individuals. Chronic toxoplasmosis establishes as latent tissue cysts in the brain and skeletal muscles. In immunocompromised patients, chronic toxoplasmosis may reactivate, leading to a potentially life-threatening condition. Recently, the association between toxoplasmosis and various diseases has been shown. These span primary neuropathies, behavioral and psychiatric disorders, and different types of cancer. Currently, a direct pre-clinical or clinical molecular connotation between toxoplasmosis and most of its associated diseases remains poorly understood. In this review, we provide a comprehensive overview on Toxoplasma-induced and associated diseases with a focus on available knowledge of the molecular players dictating these associations. We will also abridge the existing therapeutic options of toxoplasmosis and highlight the current gaps to explore the implications of toxoplasmosis on its associated diseases to advance treatment modalities.

Stable and ancient endocytic structures navigate the complex pellicle of apicomplexan parasites

“…are a leading cause of diarrhea morbidity and mortality in children younger than 5 years (Khalil et al, 2018; Striepen, 2013), and Toxoplasma gondii is the most prevalent human parasite estimated to infect a third of the world’s population (Havelaar et al, 2015). While in most adults Toxoplasma does not cause serious illness, it can cause life-threatening congenital toxoplasmosis, fetal malformation and abortion, blindness, and encephalitis, with immunocompromised individuals most susceptible (Daher et al, 2021; Montoya and Liesenfeld, 2004). Other members of Apicomplexa infect economically important livestock through which they also have major impact on human wellbeing (MacGregor et al, 2021).…”

Emulating interactions between microorganisms and tumor microenvironment to develop cancer theranostics

“…Traditionally, protozoa are parasites not only known as pathogenic factors but also play tumorigenic roles. The oncogenic roles of protozoa are mainly manifested in stimulating inflammation, modulating cytokine/chemokine networks, and triggering the response of immune cells 112 . For instance, the interleukin-12 triggered by Toxoplasma gondii stimulates T cells and natural killer (NK) cells in promoting cancer 112 (Table 3 ) .…”

“…The oncogenic roles of protozoa are mainly manifested in stimulating inflammation, modulating cytokine/chemokine networks, and triggering the response of immune cells 112 . For instance, the interleukin-12 triggered by Toxoplasma gondii stimulates T cells and natural killer (NK) cells in promoting cancer 112 (Table 3 ) . Recently, studies show that the functions of microorganisms introduced into TME play anti-tumorous roles, which we are discussed in the next section.…”

“…Leukocytes infected by Theileria annulate and Theileria parva potentially express cancer hallmarks including hypoxia inducible factor-1 alpha (HIF1α), transforming growth factor-beta (TGF-β), telomerase reverse transcriptase (TERT), murine double minute 2 (MDM2), nuclear factor-k-gene binding (NF-kB), T. annulata prolyl isomerase I gene (TaPIN1), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α) and inhibitor of apoptosis protein (IAP), which are potential chemotherapeutic targets for cancer therapy 74 . Likewise, Toxoplasma gondii and Toxoplasma gondii -derived molecules stimulate or block multiple signaling pathways such as TNF-α, NF-kB activity in modulating tumor microenvironment 112 . Epimastigotes of Trypanosoma cruzi as vaccination could systematically activate macrophages, dendritic cells, CD4+ and CD8+ T cells, thereby increasing the NADPH oxidase activity to inhibit carcinogenesis (Figure 13 ) 36 .…”

Impact of Plant-Based Foods and Nutraceuticals on Toxoplasma gondii Cysts: Nutritional Therapy as a Viable Approach for Managing Chronic Brain Toxoplasmosis

“…The strong tropism and persistence of T. gondii cysts in the brain confirm that CNS toxoplasmosis impairs the complex brain functioning. Human infection produces a gamut of clinical manifestations, ranging from longterm behavioural and cognitive alterations, to mortality following reactivation of encysted bradyzoites upon immunosuppression (36).…”