Community Research and Development Information Service - CORDIS

  • European Commission
  • CORDIS
  • Projects and Results
  • Mid-Term Report Summary - HOSTINGTOXO (Toxoplasma gondii secretes an armada of effector proteins to co-opt its host cell transcriptome and microRNome to promote sustained parasitism)
ERC

HostingTOXO Report Summary

Project ID: 614880
Funded under: FP7-IDEAS-ERC
Country: France

Mid-Term Report Summary - HOSTINGTOXO (Toxoplasma gondii secretes an armada of effector proteins to co-opt its host cell transcriptome and microRNome to promote sustained parasitism)

The project HostingToxo focuses on elucidating the molecular mechanisms underlying virulence and development of the intracellular protozoan parasite Toxoplasma gondii. Toxoplasma is a significant pathogen in its own right, causing congenital birth defects and opportunistic infection in AIDS patients, but it also serves as an informative model for less tractable parasites such as those causing malaria. Many aspects of the biology of Toxoplasma are poorly understood in terms of host range, pathogenicity, and transmission. As an obligate intracellular parasite, Toxoplasma has evolved a repertoire of strategies to fine-tune the cellular environment in an optimal way to promote growth and persistence in host tissues hence increasing the chance to be transmitted to new hosts. Short and long-term intracellular survival is associated with Toxoplasma ability to both evade the host deleterious immune defences and to stimulate a beneficial immune balance by governing host cell gene expression. Pathogen–host interactions involve processes of microbial offence that are usually driven by molecules delivered directly into host cells and of host defence in response to the former. It is only recently that Toxoplasma secretory organelle-resident proteins (namely ROP or GRA) responsible for driving these transcriptional changes have been identified. Over the last three years, we made seminal contributions that established critical roles in both acute and chronic (latent) infection for secreted effectors belonging to a subfamily of GRA proteins, exemplified with the GRA16 and GRA24 members. These effectors are singularly exported beyond the vacuole-containing parasites and reach the host cell nucleus to reshape the host (epi)genetic program. We aim to study the modus operandi of these effectors and particularly their possible implications in immune evasion and parasite persistence. HostingToxo is significant both from a basic science as well as a clinical perspective. The elucidation of molecular mechanisms underlying host-parasite interaction in Toxoplasma is revealing novel avenues of therapeutic relevance. Additionally, Toxoplasma is an early-branching eukaryotic cell, and dissecting the molecular basis of gene regulation in such a “living fossil” provides valuable information as to how these systems evolved.

Reported by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top