Persistence of Toxoplasma gondii in the central nervous system: a fine‐tuned balance between the parasite, the brain and the immune system

Abstract

SUMMARYUpon infection of humans and animals with Toxoplasma gondii, the parasites persist as intraneuronal cysts that are controlled, but not eliminated by the immune system. In particular, intracerebral T cells are crucial in the control of T. gondii infection and are supported by essential functions from other leukocyte populations. Additionally, brain-resident cells including astrocytes, microglia and neurons contribute to the intracerebral immune response by the production of cytokines, chemokines and expression of immunoregulatory cell surface molecules, such as major histocompatibility (MHC) antigens. However, the in vivo behaviour of these individual cell populations, specifically their interaction during cerebral toxoplasmosis, remains to be elucidated. We discuss here what is known about the function of T cells, recruited myeloid cells and brain-resident cells, with particular emphasis on the potential cross-regulation of these cell populations, in governing cerebral toxoplasmosis.

Infectious immunity in the central nervous system and brain function

“…CNS invasion by T. gondii 121 leads to infection of all neural cell types, most of which are promptly cleared of parasite via astrocyte and microglial expression of T cell chemoattractants CCL5, CXCL9 and CXCL10, that recruit IFN-γ-expressing CD4 + and CD8 + T cells directed at T. gondii antigens 122 . Neurons remain latently infected with slowly replicating bradyzoites throughout the life of the host.…”

Behavior of Neutrophil Granulocytes during Toxoplasma gondii Infection in the Central Nervous System

“…Cyst formation within neurons undergoing a stress-mediated response is followed by ongoing basal inflammation, establishing a chronic persistent infection (Parlog et al, 2014; Blanchard et al, 2015). Chronic cerebral toxoplasmosis is characterized by the activation of resident cells such as microglia and astrocytes, which carry out distinct antiparasitic functions (Strack et al, 2002; Schluter et al, 2003; Drögemüller et al, 2008; Kamerkar and Davis, 2012; Cabral et al, 2016).…”

Neurophysiological Changes Induced by Chronic Toxoplasma gondii Infection

“…Based on these, it remains unclear how a chronic immune response could induce the specific behavioral and neurophysiological changes observed during T. gondii infection. Indeed, the specific “fatal feline” attraction and other behavioral changes are only observed following an established chronic T. gondii infection, typically with T. gondii infection 60 days post infection, at which point the host immune response is weakest [40]. The loss of fear phenotype was even observed in mice infected with an attenuated T. gondii strain after clearance of the parasite and when no immune response was detectable [41].…”