Dissemination of Toxoplasma gondii to immunoprivileged organs and role of Toll/interleukin-1 receptor signalling for host resistance assessed by in vivo bioluminescence imaging.
Toxoplasma gondii infection can lead to life-threatening systemic disease in the immunocompromised individual and in the developing fetus. Despite intensive investigation in animal models of toxoplasmosis, the processes leading to systemic dissemination remain poorly characterized. In the present study, in vivo bioluminescence imaging (BLI) was applied to the Toxoplasma mouse model to study the dynamics of infection in real time. Photon emission analyses revealed rapid dissemination of parasites in the organism and dissemination to immunoprivileged organs (brain, eyes and testes). Spatio-temporal analysis by BLI in individual mice showed that the virulent RH strain (type I) and the non-virulent ME49/PTG strain (type II) disseminate widely, but the virulent RH strain (type I) exhibits a more dramatic expansion of parasite biomass. Assessment by BLI of the Toll/interleukin-1 receptor (TIR) signalling pathway in host resistance to T. gondii revealed that signal transduction to the adaptor protein MyD88 is probably mediated by Toll-like receptor(s) rather than by IL-1R or IL-18R signalling. However, TLR1(-/-), TLR2(-/-), TLR4(-/-), TLR6(-/-) and TLR9(-/-) animals did not exhibit increased susceptibility to infection. These results suggest that intricate mechanisms regulate TIR-mediated responses during Toxoplasma infection.
Hitziger
Niclas
N
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
Dellacasa
Isabel
I
Albiger
Barbara
B
Barragan
Antonio
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D020170:Caspase 1 / Q000235:genetics; D007113:Immunity, Innate; D008163:Luminescent Measurements; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D015398:Signal Transduction; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014122:Toxoplasma / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000469:parasitology
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D020170:Caspase 1