**Abstract**

*Toxoplasma gondii* is a zoonotic protozoan parasite that causes mortality because of significant neuropathology. It is widespread in neonatal infections. Although the neuroimmunopathogenesis of toxoplasmic encephalitis (TE) has been studied for many years, it is still not completely understood, showing the disease's severity. The urge to write this chapter comes at this stage. The sections covered in this chapter show the pathogenesis that has been established and characterized so far. The involvement of astrocytes and microglia in the development of neuropathology, which begins with tachyzoites crossing the blood-brain barrier during acute infection, has been explored. The molecular mechanism between schizophrenia and TE has been thoroughly proven. Uncovering the molecular pathogenesis of TE is critical for both understanding neuropathology and elucidating the link between neuropsychiatric diseases. Each part covered here is expected to contribute to developing novel therapeutic agents for the treatment and maybe prevention of neuropathology. The pathogenesis of the steady progression of encephalitis has been meticulously revealed. Thus, this chapter will offer significant insight into developing novel treatments for all organisms suffering from this disease.

**Keywords:** *T. gondii*, immunopathogenesis, neuropathology, toxoplasmic encephalitis, cerebral toxoplasmosis

## **1. Introduction**

*Toxoplasma gondii* (*T. gondii*), an obligate intracellular protozoan parasite, is closely related to public health because its zoonotic nature infects all warm-blooded animals [1, 2]. The severity of *T. gondii* infections is directly proportional to the infected host's immunity level. While the infection is subclinical in immunocompetent people, it causes lethal toxoplasmic encephalitis (TE) in immunocompromised people because of tissue cyst reactivation [3, 4]. *T. gondii*-related neuropathology is not only restricted to TE. *T. gondii* infections have been linked to neuropsychiatric and behavioral problems, including schizophrenia and bipolar disorders, as well as significant mental illnesses, including depression and obsessive-compulsive disorder [5–7]. Even though

#### **Figure 1.**

*The association between schizophrenia and schizophrenia mediated by T. gondii.*

neuroimmunopathogenesis and neuropsychiatric disorders in TE and the pathogenesis of neuropsychiatric disorders have been studied for a long time, they are still among the issues that are still unclear and have many questions (**Figure 1**).

This section will detail the immunopathogenesis of TE and examine potential mechanisms. Thus, it will shed light on the researchers' goals about what should be considered in the management of the TE process and what should be focused on in future studies. In addition, the intricate criteria needed for the differential diagnosis will be thoroughly covered. Therefore, considering the neuroimmunopathogenesis of the disease and the diagnosis concurrently will facilitate a better understanding of TE.

Tachyzoites, the active life form of *T. gondii*, cannot be entirely eliminated in the brain, unlike in other organs, despite activating a robust immune system upon reaching the brain. At this stage, they convert into a bradyzoite form inside a tissue cyst and continue to grow as a chronic infection, presenting no symptoms throughout the host's life [2, 8]. To reach the brain, this tissue cyst stage must first cross the bloodbrain barrier (BBB). This point, the BBB's transitional phase, will be considered the first step (**Figure 2**).

#### **2. Why is toxoplasmic encephalitis so important?**

Toxoplasmosis is far more dangerous in immunocompromised people than in healthy people. Multiple organ involvement is possible in cases of acute toxoplasmosis

## *Neuroimmunopathology in Toxoplasmic Encephalitis DOI: http://dx.doi.org/10.5772/intechopen.109341*

#### **Figure 2.**

*The T. gondii life cycle. There are two phases in the life cycle: sexual in the definitive host and asexual in intermediate hosts. Unsporulated oocysts are shed in the cat's feces. Intermediate hosts get infected after eating contaminated food or drink. Oocysts evolve into tachyzoites in the small intestine after consumption. When the host's immune system is compromised, tachyzoites induce the acute stage of infection and develop into tissue cyst bradyzoites. Bradyzoites may either remain dormant for the host's life or convert to tachyzoites. Consuming undercooked meat with tissue cysts is one of the primary transmission routes in humans. Clinical signs of the disease include encephalitis, schizophrenia, bipolar disorders, depression, obsessive-compulsive disorders, retinochoroiditis, myocarditis, and fetal abnormalities following transplacental infection in immunocompromised people.*

in immunocompromised people. Systemic diseases are often observed with severe pneumonia and retinochoroiditis, but encephalitis is the most common clinical finding [9]. The neuroimmunopathogenesis should be fully explained at this point. There is evidence that toxoplasmosis can be reactivated in people with certain cancer types, including lymphoma, leukemia, and myeloma [10–12]. Organ transplantation also poses a significant risk of toxoplasmosis, which can be fatal. For example, transplanting a *T. gondii*-infected organ to an immunocompromised patient may reactivate the organ's latent infection. Furthermore, reactivating latent *T. gondii* infection because of immunosuppressive treatment after organ transplantation can cause a fatal condition [13]. Importantly, deaths have been reported in Acquired Immune Deficiency Syndrome (AIDS) patients with CD4 T lymphocyte cell counts <200 cells/μL and severe immunosuppression, resulting in the formation of reactivation-related TE [14, 15]. It has been reported, for example, that TE develops in approximately 30–40% of immunocompromised *T. gondii* seropositive ADIS individuals [16]. It is clear that this rate is extremely high. Actually, TE is quite crucial for patients of all ages. To differentiate between patients, it is evident that immunocompromised individuals are at a higher risk. A thorough analysis of the disease's molecular pathogenesis is required at this point. Otherwise, deaths caused by TE make us to disregard the primary disease.
