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- W4313365997 abstract "Abstract After infection with the obligate intracellular protozoan parasite Toxoplasma gondii (T. gondii) the production of cytokines (especially Interferon γ (IFNγ)) induces potent cell autonomous effector mechanisms which can control the pathogen. Lymphotoxin β receptor (LTβR) mediated signalling plays an important role in the efficient initiation of innate and adaptive host responses to a variety of pathogens. Therefore, the immune response to T. gondii infection was analyzed in vivo and in vitro in LTβR deficient (LTβR−/−) and wildtype mice (WT) mice. Compared to WT mice, LTβR−/− mice showed an increased parasite burden and a markedly increased mortality in the acute phase of T. gondii infection. FACS analysis revealed that while these mice are generally able to generate T. gondii specific CD8+ T cells this does not seem sufficient for clearing the infection. Tissue and serum of LTβR−/− mice revealed deregulated cytokine expression patterns and production, particularly regarding interferons and interleukins. Since IFNγ mediated upregulation of murine guanylate-binding proteins (mGBPs) is essential for parasite clearance, expression and localization of mGBPs was evaluated. In vivo, delayed/reduced up-regulation of mGBPs expression was observed, whereas initial in vitro experiments in LTβR−/− fibroblasts demonstrated that mGBPs can be upregulated after IFNγ treatment and are able to localize at the parasitophorous vacuole. These data suggest that defects in cytokine signalling, especially IFNγ deregulation, may contribute to the decreased survival rates of LTβR−/− mice in T. gondii infection. New insights into the pathology of T. gondii could provide new therapeutic strategies for the treatment of human toxoplasmosis." @default.
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- W4313365997 date "2019-05-01" @default.
- W4313365997 modified "2023-10-14" @default.
- W4313365997 title "Lymphotoxin β receptor: A crucial role in <i>Toxoplasma gondii</i> infection" @default.
- W4313365997 doi "https://doi.org/10.4049/jimmunol.202.supp.190.87" @default.
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