IFN-gamma-regulated Toxoplasma gondii distribution and load in the murine eye.
OBJECTIVE
To establish a mouse model of ocular toxoplasmosis in both wild type (WT) and immunocompromised hosts and to clarify the effects of interferon (IFN)-gamma on the infectivity of Toxoplasma gondii in various parts of the eye.


METHODS
Susceptible WT C57BL/6, resistant WT BALB/c, and IFN-gamma knockout (GKO) mice were infected with cysts of T. gondii perorally. The tissues were harvested for molecular and histopathologic studies. Analysis included a quantitative competitive polymerase chain reaction (QC-PCR) assay and reverse transcription (RT)-PCR for IFN-gamma and stage conversion markers. All animals underwent ophthalmic examinations including fluorescein angiography (FA).


RESULTS
In WT C57BL/6 mice, T. gondii was detected in tissue in the following order: brain, retina, choroid, sclera, and optic nerve (ON). The highest T. gondii load was observed in the posterior retina, and was much greater than that in WT BALB/c mice. In GKO mice, disseminated infection was evident, and the T. gondii load was highest in the choroid and ON. IFN-gamma mRNA expression in WT C57BL/6 mice was higher than that in WT BALB/c mice after infection. Tachyzoites existed in GKO mice, whereas bradyzoites existed in WT C57BL/6 mice. FA showed dye leakage from the retinal capillaries of GKO mice.


CONCLUSIONS
The T. gondii load in the retina in the susceptible WT strain continued to increase, unlike in the resistant WT strain. IFN-gamma was shown to regulate the T. gondii load and interconversion in the eye. A toxoplasmic vasculitis model was established with GKO mice and assay systems with QC-PCR and FA.
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D005123:Eye / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D005451:Fluorescein Angiography; D050890:HSP30 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D031300:Retinal Vasculitis / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014122:Toxoplasma / Q000302:isolation & purification*; D014126:Toxoplasmosis, Ocular / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology
D000953:Antigens, Protozoan; C106179:BAG1 protein, Toxoplasma; D050890:HSP30 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; C047168:SAG1 antigen, Toxoplasma; D007371:Interferon-gamma