Toxoplasmosis of the central nervous system: Manifestations vary with immune responses

Abstract

Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), which affects one third of the global human population and commonly involves the central nervous system (CNS)/brain despite the so-called CNS immune privilege. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of CNS toxoplasmosis are linked to individual immune responses including the CNS infiltration of T-cells that are thought to prevent the disease. In patients with autoimmune diseases, immune status is complicated mainly byimmunosuppressant and/or immunomodulatory treatment but typically accompanied by infiltration of T-cells that supposedly fight against toxoplasmosis. In this article, we review characteristics of CNS toxoplasmosis comparatively in immunocompromised patients, immunocompetent patients, and patients with coexisting autoimmune diseases, as well as CNS immune responses to toxoplasmosis with a representative case to demonstrate brain lesions at different stages. In addition to general understanding of CNS toxoplasmosis, our review reveals that clinical manifestations of CNS toxoplasmosis are commonly nonspecific, and incidental pathological findings of TG infection are relatively common in immunocompetent patients and patients with autoimmune diseases (compared to immunocompromised patients); CNS immune responses such as T-cell infiltrates vary in acute and chronic lesions of brain toxoplasmosis.

Targeted Transcriptomic Analysis of C57BL/6 and BALB/c Mice During Progressive Chronic Toxoplasma gondii Infection Reveals Changes in Host and Parasite Gene Expression Relating to Neuropathology and Resolution

“…The establishment and maintenance of chronic infection involves complex changes as infection progresses from parasite entry and formation of cysts early during infection to long-term control of encysted parasites via immune cell recruitment and cytokine production leading to subtle worsening of neuropathology as infection progresses through the mid-and late chronic stages (Liesenfeld et al, 1996;Denkers, 1999;Lee and Kasper, 2004;Lachenmaier et al, 2011;Feustel et al, 2012;Lilue et al, 2013;Hong et al, 2017;Radke et al, 2018;Graham et al, 2020;Mukhopadhyay et al, 2020). Our chosen timepoints represent each of these stages to capture as much directional change in gene expression as possible.…”

“…At this point in chronicity, both innate and adaptive peripheral immune cells have been in the brain for some time and are constantly maintaining the balance between pro-and anti-inflammatory cytokine production. In addition, subtle neuropathology is commonly seen as noted by changes in morphology and function of both infected and non-infected neurons and changes in glia (David et al, 2016;Graham et al, 2020). Control of infection is maintained for the lifetime of the host and pathology at this stage can vary depending on the genetics of the parasite as well as the background of the host (Liesenfeld et al, 1996;Denkers, 1999;Lee and Kasper, 2004;Lilue et al, 2013;Mukhopadhyay et al, 2020).…”

Cerebral toxoplasmosis in HIV-infected patients: a review

“…In vivo and in vitro experiments suggest that T. gondii invades the host blood–brain barrier through three possible mechanisms ( Figure 1 ). First, it uses immune cells, such as macrophage, neutrophils, dendritic cells (DCs), and monocytes, to spread and persistently reside in neural and other brain cells through the Trojan horse mechanism [ 14 , 18 , 19 ]. Second, the extracellular tachyzoites transmigrate paracellularly through tight junctions between endothelial cells [ 20 ].…”

Cerebral Toxoplasmosis as an Uncommon Complication of Biologic Therapy for Rheumatoid Arthritis: Case Report and Review of the Literature

“…Toxoplasmosis is one of the most common opportunistic infections and parasitic zoonoses worldwide. It is caused by the intracellular protozoan parasite Toxoplasma gondii (TG), usually hosted in cats and believed to infect about one third of the world’s population [ 1 ]. Human infection normally occurs following ingestion of water and food contaminated with cat feces or ingestion of toxoplasma cysts in undercooked meat or vegetables [ 2 , 3 ].…”

“…Primary infection in immunocompetent patients is usually asymptomatic or presents as a self-limiting illness. Clinical disease is usually seen following reactivation of latent TG infection in immunocompromised patients, in which dormant bradyzoites transform into rapidly dividing tachyzoites (phenotypic switching) [ 1 , 4 ]. In these cases, toxoplasmosis may cause life-threatening disease, especially with central nervous system (CNS) involvement [ 1 ].…”