A new perspective on anti-Toxoplasma immunity.


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2011-2015

FUNDING AMOUNT

843346 GBP

ABSTRACT

Toxoplasma gondii is a protozoan parasite that infects a broad range of warm-blooded hosts (human seroprevalence: 30 %). How Toxoplasma maintains the balance between intracellular survival and elimination by the host remains unclear. IFN- controls the elimination of Toxoplasma: it restricts intracellular parasite replication and helps eliminate intracellular Toxoplasma. I shall identify novel aspects of host resistance to Toxoplasma, by defining the connections between innate and adaptive immuni ty. I have identified three new Toxoplasma-specific CD8 T cell epitopes. Transnuclear mice bearing T cell receptors specific for all four currently known Toxoplasma epitope-MHC complexes were generated. With these tools, I shall study the antigen processing requirements of these epitopes, both in vitro and in vivo. I shall study a poorly understood class of IFN- upregulated GTPases (p65 GTPases), hypothesized to exert an anti-parasitic effect, in the context of facilitated antigen presentation. I shall examine their possible involvement in fusion of the parasitophorous vacuole and the endoplasmic reticulum. These studies will shed new light on immunity against Toxoplasma and so contribute to the design of more effective countermeasures, of relevance also to other apicomplexan parasites such as the causative agent of malaria, Plasmodium falciparum. More... »

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