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Infection and Immunity, April 2009, p. 1368-1375, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01450-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Trypanosoma cruzi Promotes Neuronal and Glial Cell Survival through the Neurotrophic Receptor TrkC{triangledown}

Craig Weinkauf and Mercio PereiraPerrin*

Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, Massachusetts 02111

Received 26 November 2008/ Returned for modification 13 January 2009/ Accepted 21 January 2009

Trypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial cell-derived family ligand receptors (GFR{alpha}). 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.

* Corresponding author. Mailing address: Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111. Phone: (617) 636-2933. Fax: (617) 636-6849. E-mail: Mercio.perrin{at}tufts.edu

{triangledown} Published ahead of print on 29 January 2009.

Editor: W. A. Petri, Jr.

Infection and Immunity, April 2009, p. 1368-1375, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01450-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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