The Chagas' disease parasite Trypanosoma cruzi exploits nerve growth factor receptor TrkA to infect mammalian hosts.
Trypanosoma cruzi, the agent of Chagas' disease, is an obligate intracellular parasite that invades various organs including several cell types in the nervous system that express the Trk receptor tyrosine kinase. Activation of Trk is a major cell-survival and repair mechanism, and parasites could use Trks to invade cells as a strategy to protect their habitat and prolong parasitism of vertebrate hosts. We show that T. cruzi binds to TrkA specifically and activates TrkA-dependent survival mechanisms. This interaction facilitates parasite adherence and promotes efficient invasion of neuronal, epithelial, and phagocytic cells via a process that requires TrkA kinase activity. Diffusible TrkA and TrkA-blocking agents neutralized infection in cellular and animal models of acute Chagas' disease, suggesting cellular receptors as therapeutic targets against parasitic diseases. Thus, TrkA, the nerve growth factor receptor commonly associated with neural survival and protection, may also underlie clinical progression of an important human parasitic disease.
de Melo-Jorge
Milena
M
Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.
PereiraPerrin
Mercio
M
D000818:Animals; D014355:Chagas Disease / Q000469:parasitology* / Q000503:physiopathology / Q000635:transmission*; D006801:Humans; D008322:Mammals; D009420:Nervous System / Q000469:parasitology; D009424:Nervous System Physiological Phenomena; D009474:Neurons / Q000469:parasitology; D016716:PC12 Cells; D051381:Rats; D020917:Receptor, trkA / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014346:Trypanosoma brucei brucei / Q000472:pathogenicity / Q000502:physiology*
D020917:Receptor, trkA