Abstract
Ocular toxoplasmosis (OT), mostly retinochorioditis, is a major feature of infection with the protozoan parasite Toxoplasma gondii. The pathophysiology of this infection is still largely elusive; especially mouse models are not yet well developed. In contrast, numerous in vitro studies showed the highly Toxoplasma strain dependent nature of the host-parasite interactions. Some distinct polymorphic virulence factors were characterized, notably the rhoptry protein ROP16. Here, we studied the strain-dependent pathophysiology in our OT mouse model. Besides of two wild type strains of the canonical I (RH, virulent) and II (PRU, avirulent) types, we used genetically engineered parasites, RHΔROP16 and PRU ROP16-I, expressing the type I allele of this virulence factor. We analyzed retinal integrity, parasite proliferation and retinal expression of cytokines. PRU parasites behaved much more virulently in the presence of a type I ROP16. In contrast, knockout of ROP16 in the RH strain led to a decrease of intraocular proliferation, but no difference in retinal pathology. Cytokine quantification in aqueous humor showed strong production of Th1 and inflammatory markers following infection with the two strains containing the ROP16-I allele. In strong contrast, immunofluorescence images showed that actual expression of most cytokines in retinal cells is rapidly suppressed by type I strain infection, with or without the involvement of its homologous ROP16 allele. This demonstrates the particular immune privileged situation of the retina, which is also revealed by the fact that parasite proliferation is nearly exclusively observed outside the retina. In summary, we further developed a promising OT mouse model and demonstrated the specific pathology in retinal tissues.
Highlights
Toxoplasma gondii is a ubiquitous apicomplexan parasite, infecting a third of the human population
Ocular toxoplasmosis (OT), mainly expressed as retinochoroididitis, have gained clinical attention, as survey studies revealed an unexpected prevalence of this affection of 1–2% in Europe and North America [1], most of which cannot be attributed to congenital infection [2]
To evaluate the role of the virulence factor ROP16, we first evaluated the effect of a virulent ROP16-I allele in an avirulent type II Toxoplasma strain (PRU ROP16-I)
Summary
Toxoplasma gondii is a ubiquitous apicomplexan parasite, infecting a third of the human population. Several types of glial cells help to maintain an anti-inflammatory environment and to preserve the integrity of the neuronal cells. The retinal architecture is usually visibly distorted, local glial cells activated and inflammatory leukocytes attracted [4]. We previously demonstrated this for T. gondii infection [5]. In order to investigate the pathophysiological mechanisms, we previously characterized a murine OT model of intravitreal injection of the replicative tachyzoite stage in basic parasitological and immunological terms [6] and demonstrated the importance of the inflammatory Th17 pathway in infection with the relatively avirulent type II parasites [7]. We used and further developed this model in the present study
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