A Highly Conserved Haplotype Directs Resistance to Toxoplasmosis and Its Associated Caspase-1 Dependent Killing of Parasite and Host Macrophage

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Toxoplasmosis is a ubiquitous parasitic infection causing a wide spectrum of diseases. It is usually asymptomatic but can lead to severe ocular and neurological disorders. The host factors that determine natural resistance to toxoplasmosis are yet poorly characterized. Among the animal models to study susceptibility to toxoplasmosis, rats develop like humans a subclinical chronic infection. The finding of a total resistance in the LEW rat strain has allowed genetic studies leading to the identification of Toxo1, a unique locus that controls the outcome of toxoplasmosis. In this report, a panel of recombinant inbred rat strains was used to genetically reduce the Toxo1 locus, on chromosome 10, to a limited region containing 29 genes. This locus is highly conserved among five resistant, by comparison to four susceptible, rat strains, indicating that refractoriness to toxoplasmosis could be predicted. The Toxo1-controlled refractoriness depends on the ability of macrophages to restrict parasite proliferation and the rapid death of both T. gondii and host macrophages in vitro. The NOD-like receptor NLRP1a/Caspase-1 pathway is the best candidate to mediate the parasite-induced cell death. Our data represent new insights towards the identification of a major pathway of innate immunity that protects from toxoplasmosis.

Vyšlo v časopise: A Highly Conserved Haplotype Directs Resistance to Toxoplasmosis and Its Associated Caspase-1 Dependent Killing of Parasite and Host Macrophage. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1004005
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004005

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