Format

Send to

Choose Destination
Infect Immun. 2009 Apr;77(4):1368-75. doi: 10.1128/IAI.01450-08. Epub 2009 Jan 29.

Trypanosoma cruzi promotes neuronal and glial cell survival through the neurotrophic receptor TrkC.

Author information

1
Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

Abstract

Trypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial cell-derived family ligand receptors (GFRalpha). However, these receptors are expressed by only a subset of neurons and at low levels or not at all in glial cells. Thus, T. cruzi might exploit an additional neurotrophic receptor(s) to maximize host-parasite equilibrium in the nervous system. We show here that T. cruzi binds TrkC, a neurotrophic receptor expressed by glial cells and many types of neurons, and that the binding is specifically inhibited by neurotrophin-3, the natural TrkC ligand. Coimmunoprecipitation and competition assays show that the trans-sialidase/parasite-derived neurotrophic factor (PDNF), previously identified as a TrkA ligand, mediates the T. cruzi-TrkC interaction. PDNF promotes TrkC-dependent mitogen-activated protein kinase signaling, neurite outgrowth, and survival of genetically engineered PC12 neuronal cells and glial Schwann cells in a TrkC-dependent manner. Thus, TrkC is a new neurotrophic receptor that T. cruzi engages to promote the survival of neuronal and glial cells. The results raise the possibility that T. cruzi recognition of TrkC underlies regenerative events in nervous tissues of patients with Chagas' disease.

PMID:
19179422
PMCID:
PMC2663174
DOI:
10.1128/IAI.01450-08
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center