PROJECT: JTC2014: NEUINF

Master regulators of neuroinflammation in parasitic brain infections

Abstract

In this integrated project we will compare the consequences of neuro-immune responses in models of parasite infections of the brain with 1) the extracellular African trypanosomes which invades into the brain; 2) the intracellular malaria parasites which infect red blood cells that attach to cerebral endothelial cells but do not penetrate into the brain and 3) Toxoplasma, which spread via monocytes and dendritic cells to the brain to infect both glial cells and neurons. We will compare these mechanisms with those involved in the control of neuroinflammation after the infection with rabies virus, that has evolved robust strategies to dampen inflammation of the brain. We have discovered rabies virus derived “anti-inflammatory peptides”. Here we will test their efficacy as anti parasitic drug in models of parasitic brain infection that induce neuroinflammation. Specifically we will study 1. The relevance of IFN-αβ in neuroinflammation induced by brain parasitic infections. 2. The role of TRAF3 in regulation of neuroinflammation, neuroinvasion and intracerebral parasite growth control 3. The molecular characterization and properties of rabies-virus derived anti-inflammatory molecules, and their ability to regulate neuroinflammation due to different parasitic infection.

Keywords

Gene targeting in the brain, Experimental models of brain infection

Call topic

Neuroinflammation

Proposed runtime

2014 - 2018

Project team

Rottenberg (Coordinator)
Sweden (SRC)
Barragan
Sweden (SRC)
Penha Gonçalves
Portugal (FCT)
Schlüter
Germany (BMBF)
Lafon
France (ANR)