Cellular and Molecular Mechanisms of Toxoplasma Gondii Infection and Its Role in Neuroinflammation

Toxoplasma gondii is a protozoan parasite that is an obligate intracellular animal and can infect almost any type of nucleated cell, but it shows a specific predilection to neural and muscular tissue. Chronic infection is also described as development of tissue cysts within the brain in which the parasite exists in a latent form and can lead to the development of long term neuropathological changes. This review presents an overview of the most important cellular and molecular processes that are involved in the T. gondii infection and the contributions these would make to neuroinflammation. After host cell invasion, the parasite invades to form a special parasitophorous vacuole which eludes lysosomal degradation and the regulation of host signaling pathways by releasing effector proteins in rhoptries and dense granules. Such effectors regulate immune reactions by changing NF-κB, STAT and interferon-7-mediated pathways to favor parasite survival as well as to influence the inflammatory milieu. The infection within the central nervous system causes the activation of the microglia and astrocytes resulting in the release of pro-inflammatory cytokines including interleukin-1β, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma. Although these reactions are necessary to regulate the replication of the parasites, the prolonged activation is involved in the formation of oxidative stress, synaptic dysfunction, and neuronal damage. The impairment of blood-brain barrier and changes in neurotransmitter systems, especially to glutamate and dopamine systems also contribute to the worsening of neuroinflammatory mechanisms. Parasite-derived protein molecular interactions with the immune mediators are key in the regulation of parasite survival and pathology mediated by the immune system. The knowledge of these mechanisms is vital in the understanding of the relationship between chronic toxoplasmosis and neuropsychiatric disorders and can help to develop specific immunomodulatory and antiparasitic strategies.