TOXOSHEEP · Study of the molecular mechanisms underlying Toxoplasma-induced early abortions in a pregnant sheep model of infection

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Project objective

Toxoplasma gondii is a major cause of abortion in humans and livestock, thereby producing a significant public health hazard and economic losses. Most of Toxoplasma’s virulence factors have been explored using mouse models; however, the murine immune response differs significantly from that of humans and farm animals. Despite Toxoplasma’s enormous economic and health implications, little is known about the factors that cause foetal mortality and vertical transmission in humans or livestock. The goal of this ambitious project is to close this gap in knowledge by studying the mechanisms involved in the early abortion during the acute phase of toxoplasmosis in a standardised animal model relevant for humans and livestock. We hypothesise that by using a pregnant sheep model, the molecular mechanisms underlying the parasite-induced inflammation associated with early abortions can be identified. To this end, we will first characterize the early infection dynamics, lesions, parasite burden and peripheral immune response in the dams. This will provide valuable information as to the initial immune response elicited by the parasite and how it reaches the placenta. Subsequently, we will investigate the local molecular mechanisms involved in the parasite-induced pathogenesis of early abortions by combining novel immunohistopathological and transcriptomic approaches in order to identify alterations of gene expression and biological pathways in the materno-foetal interface. The results derived from this proposal will significantly advance the understanding of the mechanisms of Toxoplasma early abortions and help in the design of transmission-blocking vaccines or drugs. Because Toxoplasma has been associated with women who had spontaneous abortions, it is likely that these mechanisms are shared with humans. Thus, these results will not only produce economic savings in the livestock industry but will also directly improve human health.

Original text from CORDIS.

Participants

• UNIVERSIDAD COMPLUTENSE DE MADRID · MadridCoordinatorSpain

Links

• View on CORDIS
• DOI: 10.3030/101028616