Tissue cyst rupture in mice chronically infected withToxoplasma gondii

Abstract

The incidence and effect of tissue cyst rupture in the brains of mice chronically infected with Toxoplasma gondii was studied by immunocytochemistry and electron microscopy. Cyst rupture was extremely rare (2 of 750 tissue cysts) irrespective of the interval post-infection. The event was associated with a rapid cell-mediated immune response, giving rise to microglial or inflammatory nodules. Macrophages were observed to engulf and degrade the cystozoites and cyst debris. Initially, the nodules contained large amounts of immunologically reactive material, but this was degraded with the majority (94%) of lesions containing no recognizable parasites or Toxoplasma antigens. There was little evidence of parasite multiplication or new cyst formation associated with cyst rupture. This study shows that although intermittent cyst rupture occurs, in immunocompetent individuals the immune response limits the potential damage from the release of large numbers of infective organisms to small microglial/inflammatory nodules.

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

“…In addition, bradyzoites within brain cysts are surrounded by a cyst wall and, thus, very little parasite material may escape into the cytoplasm of the cyst-containing host cell. We also observed large aggregates of CD11b ϩ cells near isolated parasites, but not intact cysts, consistent with previous reports based on light and electron microscopy (32,59). Interestingly, in those earlier studies examples were noted in which a small numbers of macrophages surrounded a cyst that was within a host cell with a disrupted membrane, suggesting an early macrophage response to cyst rupture (59).…”

“…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.…”

“…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).…”

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

“…In immunocompromised individuals such as those with AIDS and organ transplants, cysts can rupture resulting in release of bradyzoites, conversion of bradyzoites into tachyzoites, and proliferation of tachyzoites, which can cause lifethreatening toxoplasmic encephalitis (Israelski and Remington 1993). Even in immunocompetent host, T. gondii cysts occasionally rupture during the chronic stage of infection (Ferguson et al 1989). In these cases, tachyzoite growth is controlled by the host's immune response, but the parasite is most likely able to form small numbers of new cysts.…”

Toxoplasma gondii: 1908-2008, homage to Nicolle, Manceaux and Splendore

“…The question was: "What happens in such a situation in an immuno-competent individual?". An extensive search, over a number of years in chronically infected immuno-competent mice, identified a few (< 1%) rupturing tissue cysts (Ferguson et al 1989). It appears that death of the host cell unmasks the tissue cyst and results in an immediate response of the host inflammatory cells, predominately monocyte/macrophages but also neutrophils.…”