Research Article: Toxoplasma gondii: Entry, association, and physiological influence on the central nervous system

Date Published: July 20, 2017

Publisher: Public Library of Science

Author(s): Oscar A. Mendez, Anita A. Koshy, Marc-Jan Gubbels.


Toxoplasma gondii is one of the world’s most successful parasites, in part because of its ability to infect and persist in most warm-blooded animals. A unique characteristic of T. gondii is its ability to persist in the central nervous system (CNS) of a variety of hosts, including humans and rodents. How, what, and why T. gondii encysts in the CNS has been the topic of study for decades. In this review, we will discuss recent work on how T. gondii is able to traverse the unique barrier surrounding the CNS, what cells of the CNS play host to T. gondii, and finally, how T. gondii infection may influence global and cellular physiology of the CNS.

Partial Text

Toxoplasma gondii is an obligate intracellular parasite of the phyla Apicomplexa. Felids are the only definitive host for T. gondii, but T. gondii has a wide intermediate host range and has been documented to naturally infect most warm-blooded animals including birds, rodents, and humans [1]. In most hosts, T. gondii establishes a life-long, latent infection in tissues such as skeletal muscle, cardiac muscle, or the central nervous system (CNS), which includes the brain, the spinal cord, and the retina. In this review, we will often use CNS interchangeably with the brain, in which the majority of the work on T. gondii has been done.

Given the importance of CNS persistence to clinical disease, where and how T. gondii persists in the CNS in the immunocompetent host has long been an area of interest. Human data on CNS regions “susceptible” to T. gondii primarily come from autopsies of AIDS patients. In these studies of severely immunocompromised patients, T. gondii lesions were consistently found in the cerebral cortex and basal ganglia, with fewer lesions in the cerebellum, brainstem, and spinal cord [44–46]. These data are consistent with the localization of cysts observed in rodents [47–49].

Until recently, little work had been done on how T. gondii changes CNS physiology, but in the last several years, a number of important in vivo studies have begun to address this question. A major mechanism for affecting CNS physiology would be through changes in neurotransmitters, the molecules that neurons use for interneuronal communication. In vivo measurements of neurotransmitters have primarily measured global changes within the brain, not cell-specific changes. The dopaminergic system has been of major interest because dopamine is essential for locomotor activity (movement) and various forms of learning, including fear [72]. As such, investigators have sought to implicate the dopaminergic system in infection-induced behavioral changes [9]. Several studies that directly measured CNS dopamine levels or dopamine metabolites suggest that postinfection, CNS dopamine levels increase [73,74], though another group was unable to confirm these changes [75]. One explanation for these contradictory findings is that each group used different mouse strains, which can affect the immune response to T. gondii [76,77]. As immune cells have been shown to make dopamine [78] and none of the groups determined the cellular source of the measured dopamine or metabolites, these differences might simply reflect differing levels of immune infiltration into the CNS rather than changes in the CNS dopaminergic cells or pathways.

In the last decade, important work has been done to better define many molecular and cellular aspects of the T. gondii–CNS interaction. While these studies leave a number of outstanding questions as noted above, they form the foundation of an exciting time in the evolution of our understanding of CNS toxoplasmosis.




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