Host Cell Preference of Toxoplasma gondii Cysts in Murine Brain: A Confocal Study

Abstract

Toxoplasma gondii is a protozoan parasite that is widely prevalent in humans and typically results in a chronic infection characterized by cysts located predominantly in the central nervous system. In immunosuppressed hosts, such as patients with HIV infection, the infection can be reactivated from the cysts in the brain resulting in a severe and potentially fatal encephalitis. Studies suggest that the chronic infection may also have neuropathological and behavioral effects in immune competent hosts. An improved understanding of tissue cyst behavior is of importance for understanding both the reactivation as well as the neurophysiological consequences of chronic infection. In vivo studies have identified neurons as host cells for cysts but in vitro studies have found that astrocytes can also foster development of the cysts. In this study we have addressed the question of which neural cell tissue cysts of T. gondii reside during chronic infection using a mouse model. Mice were infected with Me49 Strain T. gondii and the intracellular localization of the cysts analyzed during the development and establishment of a chronic infection at 1, 2, and 6 months post infection. Brains were fixed, cryosectioned, and stained with FITC-Dolichos biflorans to identify the Toxoplasma cysts and they were labeled with cell specific antibodies to neurons or astrocytes and then analyzed using confocal fluorescence microscopy. Cysts were found to occur almost exclusively in neurons throughout chronic infection. No cysts were identified in astrocytes, using the astrocyte marker, GFAP. Astrocyte interactions with neuronal-cysts, however, were frequently observed.

In vivo effect of anti-TNF agent (etanercept) in reactivation of latent toxoplasmosis

“…They were mostly found as individual cysts either solitary or in groups. The patterns of cysts growth found in this study are consistent with other studies which found that Toxoplasma cysts in the brain grow uniformly in size up to 2-3 months post-infection and persist in the brain for many months post-infection (Melzer et al 2010).…”

Toxoplasma gondii infection and behaviour – location, location, location?

“…A number of in vitro studies have indicated that cysts can be found in astrocytes; however, in vivo studies in mice found cysts nearly exclusively in neurones in chronically infected animals, albeit with some evidence of an interaction between astrocytes and T. gondii cysts (Hermes et al, 2008;Melzer et al, 2010). In a time course of chronic infection, the majority of infected host cells in mouse brains were identified as neurones based on electron microscopy analysis (Ferguson and Hutchinson, 1987).…”

Latent Toxoplasmosis gondii: Emerging Evidence for Influences on Neuropsychiatric Disorders

“…Studies quantifying T. gondii cyst burden in multiple brain areas in rodents with chronic infection found differences in relative burden across regions, but the patterns vary considerably. 2,[4][5][6][7] Results for a few commonly reported regions are illustrated, with longer times post-infection indicated by lighter colors. Studies are separated into two histograms, based on method of quantification used.…”