Abstract
We examined the in vivo growth, dissemination, and reactivation of strains of the protozoan parasite Toxoplasma gondii using a bioluminescence-based imaging system. Two T. gondii strains, one with a highly virulent disease phenotype in mice (S23) and the other with a 1,000-fold-lower virulence phenotype (S22), were engineered to stably express the light-emitting protein luciferase. One clone of each wild-type strain was isolated, and the two clones (S23-luc7 and S22-luc2) were found to express similar levels of luciferase. Mice were infected intraperitoneally with S23-luc7 (50 or 5 parasites) or S22-luc2 (500, 50, or 5 parasites), and the progress of the infections was examined noninvasively following injection of the substrate for luciferase, D-luciferin. In mice infected with 50 S23-luc7 parasites, the parasites grew exponentially within the peritoneal cavity (as measured by light emitted from luciferase-expressing parasites) during days 1 to 10 p.i., and this proliferation continued until there was severe disease. In mice infected with 500 S22-luc2 parasites, the parasites proliferated in a fashion similar to the S23-luc7 proliferation during days 1 to 6, but this was followed by a precipitous drop in the signal to levels below the limit of detection. Using this technique, we were also able to observe the process of reactivation of T. gondii in chronically infected mice. After treatment with dexamethasone, we detected reactivation of toxoplasmosis in mice infected with S23-luc7 and S22-luc2. During reactivation, growth of S23-luc7 was initially detected primarily in the head and neck area, while in S22-luc2-infected mice the parasites were detected primarily in the abdomen. This method has great potential for identifying important differences in the dissemination and growth of different T. gondii strains, especially strains with dramatically different disease outcomes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 695-702 |
| Number of pages | 8 |
| Journal | Infection and Immunity |
| Volume | 73 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
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Bioluminescence imaging of Toxoplasma gondii infection in living mice reveals dramatic differences between strains. / Saeij, Jeroen; Boyle, Jon P.; Grigg, Michael E.; Arrizabalaga, Gustavo; Boothroyd, John C.
In: Infection and Immunity, Vol. 73, No. 2, 02.2005, p. 695-702.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bioluminescence imaging of Toxoplasma gondii infection in living mice reveals dramatic differences between strains
AU - Saeij, Jeroen
AU - Boyle, Jon P.
AU - Grigg, Michael E.
AU - Arrizabalaga, Gustavo
AU - Boothroyd, John C.
PY - 2005/2
Y1 - 2005/2
N2 - We examined the in vivo growth, dissemination, and reactivation of strains of the protozoan parasite Toxoplasma gondii using a bioluminescence-based imaging system. Two T. gondii strains, one with a highly virulent disease phenotype in mice (S23) and the other with a 1,000-fold-lower virulence phenotype (S22), were engineered to stably express the light-emitting protein luciferase. One clone of each wild-type strain was isolated, and the two clones (S23-luc7 and S22-luc2) were found to express similar levels of luciferase. Mice were infected intraperitoneally with S23-luc7 (50 or 5 parasites) or S22-luc2 (500, 50, or 5 parasites), and the progress of the infections was examined noninvasively following injection of the substrate for luciferase, D-luciferin. In mice infected with 50 S23-luc7 parasites, the parasites grew exponentially within the peritoneal cavity (as measured by light emitted from luciferase-expressing parasites) during days 1 to 10 p.i., and this proliferation continued until there was severe disease. In mice infected with 500 S22-luc2 parasites, the parasites proliferated in a fashion similar to the S23-luc7 proliferation during days 1 to 6, but this was followed by a precipitous drop in the signal to levels below the limit of detection. Using this technique, we were also able to observe the process of reactivation of T. gondii in chronically infected mice. After treatment with dexamethasone, we detected reactivation of toxoplasmosis in mice infected with S23-luc7 and S22-luc2. During reactivation, growth of S23-luc7 was initially detected primarily in the head and neck area, while in S22-luc2-infected mice the parasites were detected primarily in the abdomen. This method has great potential for identifying important differences in the dissemination and growth of different T. gondii strains, especially strains with dramatically different disease outcomes.
AB - We examined the in vivo growth, dissemination, and reactivation of strains of the protozoan parasite Toxoplasma gondii using a bioluminescence-based imaging system. Two T. gondii strains, one with a highly virulent disease phenotype in mice (S23) and the other with a 1,000-fold-lower virulence phenotype (S22), were engineered to stably express the light-emitting protein luciferase. One clone of each wild-type strain was isolated, and the two clones (S23-luc7 and S22-luc2) were found to express similar levels of luciferase. Mice were infected intraperitoneally with S23-luc7 (50 or 5 parasites) or S22-luc2 (500, 50, or 5 parasites), and the progress of the infections was examined noninvasively following injection of the substrate for luciferase, D-luciferin. In mice infected with 50 S23-luc7 parasites, the parasites grew exponentially within the peritoneal cavity (as measured by light emitted from luciferase-expressing parasites) during days 1 to 10 p.i., and this proliferation continued until there was severe disease. In mice infected with 500 S22-luc2 parasites, the parasites proliferated in a fashion similar to the S23-luc7 proliferation during days 1 to 6, but this was followed by a precipitous drop in the signal to levels below the limit of detection. Using this technique, we were also able to observe the process of reactivation of T. gondii in chronically infected mice. After treatment with dexamethasone, we detected reactivation of toxoplasmosis in mice infected with S23-luc7 and S22-luc2. During reactivation, growth of S23-luc7 was initially detected primarily in the head and neck area, while in S22-luc2-infected mice the parasites were detected primarily in the abdomen. This method has great potential for identifying important differences in the dissemination and growth of different T. gondii strains, especially strains with dramatically different disease outcomes.
UR - http://www.scopus.com/inward/record.url?scp=12844263594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12844263594&partnerID=8YFLogxK
U2 - 10.1128/IAI.73.2.695-702.2005
DO - 10.1128/IAI.73.2.695-702.2005
M3 - Article
C2 - 15664907
AN - SCOPUS:12844263594
VL - 73
SP - 695
EP - 702
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 2
ER -