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      Experimental Models of Ocular Infection with Toxoplasma Gondii

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          Abstract

          Ocular toxoplasmosis is a vision-threatening disease and the major cause of posterior uveitis worldwide. In spite of the continuing global burden of ocular toxoplasmosis, many critical aspects of disease including the therapeutic approach to ocular toxoplasmosis are still under debate. To assist in addressing many aspects of the disease, numerous experimental models of ocular toxoplasmosis have been established. In this article, we present an overview on in vitro, ex vivo, and in vivo models of ocular toxoplasmosis available to date.

          Experimental studies on ocular toxoplasmosis have recently focused on mice. However, the majority of murine models established so far are based on intraperitoneal and intraocular infection with Toxoplasma gondii. We therefore also present results obtained in an in vivo model using peroral infection of C57BL/6 and NMRI mice that reflects the natural route of infection and mimics the disease course in humans. While advances have been made in ex vivo model systems or larger animals to investigate specific aspects of ocular toxoplasmosis, laboratory mice continue to be the experimental model of choice for the investigation of ocular toxoplasmosis.

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          Most cited references 118

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          Innate immunity to Toxoplasma gondii infection.

          Toxoplasma gondii is a protozoan parasite of global importance. In the laboratory setting, T. gondii is frequently used as a model pathogen to study mechanisms of T helper 1 (TH1) cell-mediated immunity to intracellular infections. However, recent discoveries have shown that innate type 1 immune responses that involve interferon-γ (IFNγ)-producing natural killer (NK) cells and neutrophils, rather than IFNγ-producing T cells, predetermine host resistance to T. gondii. This Review summarizes the Toll-like receptor (TLR)-dependent mechanisms that are responsible for parasite recognition and for the induction of IFNγ production by NK cells, as well as the emerging data about the TLR-independent mechanisms that lead to the IFNγ-mediated elimination of T. gondii.
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            An unusually high prevalence of ocular toxoplasmosis in southern Brazil.

            Because of the frequency of ocular toxoplasmosis and its occurrence in multiple siblings in southern Brazil, a population-based household survey was performed to better understand the epidemiologic characteristics of the disease in this region. Of 1,042 individuals examined, 184 (17.7%) were deemed to have ocular toxoplasmosis on the basis of conservative assessment of ophthalmic findings. Of those with ocular toxoplasmosis, 183 (99.5%) had specific IgG antibodies, compared with only 140 of 181 age-matched control subjects (77.4%; P less than .001). The prevalence of ocular toxoplasmosis was 0.9% in 1- to 8-year-olds, 4.3% in 9- to 12-year-olds, 14.3% in 13- to 16-year-olds, and 21.3% (95% confidence interval, 18.6% to 24.2%) in all individuals 13 years or older. The prevalence of ocular toxoplasmosis in this population was more than 30 times higher than previous estimates for the same condition elsewhere. The low prevalence in the young children we studied supplements previous data suggesting that, in this population, ocular toxoplasmosis is a sequela of postnatal rather than congenital infection.
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              Immunology of Toxoplasma gondii.

              Toxoplasma gondii is an obligate intracellular parasite. Following oral infection the parasite crosses the intestinal epithelial barrier to disseminate throughout the body and establish latent infection in central nervous tissues. The clinical presentation ranges from asymptomatic to severe neurological disorders in immunocompromised individuals. Since the clinical presentation is diverse and depends, among other factors, on the immune status of the host, in the present review, we introduce parasitological, epidemiological, clinical, and molecular biological aspects of infection with T. gondii to set the stage for an in-depth discussion of host immune responses. Since immune responses in humans have not been investigated in detail the present review is exclusively referring to immune responses in experimental models of infection. Systemic and local immune responses in different models of infection are discussed, and a separate chapter introduces commonly used animal models of infection. © 2011 John Wiley & Sons A/S.
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                Author and article information

                Journal
                Eur J Microbiol Immunol (Bp)
                Eur J Microbiol Immunol (Bp)
                EUJMI
                European Journal of Microbiology & Immunology
                Akadémiai Kiadó (Budapest )
                2062-509X
                2062-8633
                04 December 2015
                December 2015
                : 5
                : 4
                : 293-305
                Affiliations
                [1 ]Institut für Mikrobiologie und Hygiene, Charité Universitätsmedizin Berlin, Germany
                [2 ] Disciplina de Anatomia Descritiva e Topográfica, Escola Paulista de Medicina, Universidade Federal de São Paulo , Brazil, Germany
                Author notes
                * Medical and Scientific Affairs, Roche Molecular Systems, 4388 Hacienda Dr., Pleasanton, CA 94588, USA; oliver.liesenfeld@ 123456roche.com
                Article
                10.1556/1886.2015.00045
                4681357
                © 2015, The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 103, Pages: 13
                Categories
                Original Article

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