A morphological study of chronic cerebral toxoplasmosis in mice: comparison of four different strains ofToxoplasma gondii

Abstract

The pathological changes, host-parasite relationship and structure of the tissue cysts in the brains of mice chronically infected with four different strains of Toxoplasma gondii were examined by light and electron microscopy. In mice infected with the mouse-adapted ME49 strain for 4, 8, 12, 16 and 25 weeks, the pathological changes consisted of moderate to severe meningitis and cuffing of blood vessels by inflammatory cells. At 4 weeks post-infection (p.i.), lymphocytes were the major cell type, but at later time points, plasma cells predominated. Large numbers of cysts were observed at between 4 and 12 weeks p.i., with a decrease being seen at 16 weeks p.i. Microglial nodules, many containing tachyzoites or bradyzoites, were present at all time points. In contrast, the three strains isolated from patients with the acquired immune deficiency syndrome (AIDS) resulted in no meningitis in two cases (DEY, DAG) and in mild meningitis in one case (WIL), although all three showed some cuffing of blood vessels. In addition, only very low numbers of cysts and nodules were observed. Ultrastructurally, the cysts of all four strains were seen to be located within host cells. The cysts of the ME49 strain differed from those of the other strains in that a proportion contained immature and dividing bradyzoites at all time points, whereas those of the other strains contained only mature bradyzoites. From the observation of nodules with parasites and cysts with immature zoites, it would appear that the ME49 strain may result in an unstable chronic infection with a continuous turnover of cysts, a feature that should be taken into consideration when this strain is used as an experimental model of chronic toxoplasmosis.

Dynamic Imaging of T Cell-Parasite Interactions in the Brains of Mice Chronically Infected withToxoplasma gondii

“…Moreover, the majority of the CD11b aggregates observed contained one or more isolated parasites (20 aggregates with a total of 28 parasites from 12 different sections) and aggregates of CD11b ϩ cells were not seen around cysts (data not shown). This is consistent with previous light microscopy studies (32,59) and implies that, like T cells, CD11b ϩ cells in the brains of chronically infected mice responded to isolated parasites rather than to intact cysts. CD11b ϩ aggregates were most prominent at late time points postinfection (19 days postinfection), whereas at earlier times postinfection parasite fluorescence was more often seen associated with isolated CD11b ϩ cells (Fig.…”

“…7C and data not shown). Previous electron microscopy studies indicated that cysts could be found within intact neurons (32), which is compatible with our observation that 25% of cysts (4/16) were surrounded by MAP2 staining (Fig. 7D and data not shown).…”

“…To characterize potential APCs, we examined fixed brain sections by confocal microscopy using Abs to CD11b, a marker expressed by monocyte/myeloid lineage cells and microglia that has been previously shown to be associated with parasites in the brains of chronically infected mice (64). In the brains of chronically infected mice we observed spherical, tightly packed aggregates of CD11b-expressing cells that may correspond to the "nodules" of leukocytes described previously (32,59) (Fig. 7Ai and Aii).…”

“…CD8 T cells typically recognize peptides derived from intracellular pathogens presented by MHC class I molecules on infected host cells. Parasites convert into bradyzoites within living host cells (30,31), and cysts within the brains of chronically infected mice reside within intact cells (32). However, whether CD8 T cells can recognize and respond directly to parasite Ags on the surface of cyst-containing cells is not known.…”

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

“…This drug was also found effective against toxoplasmosis, another common opportunistic infection in patients with AIDS (Spencer and Goa 1995). In this case, atovaquone displays a potent in vitro activity against both the tachyzoite and cyst forms of Toxoplasma gondii (Romand et al 1993;Ferguson et al 1994). …”