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.

Inactivation of protozoan parasites in red blood cells using INACTINE PEN110 chemistry.

BACKGROUND: The transmission of parasites, including Babesia, plasmodia, and Trypanosoma cruzi, via transfusions is an important public health concern. INACTINE technology is a pathogen-reduction process that utilizes PEN110, an electrophilic agent that inac-tivates a wide range of pathogens by disrupting nucleic acid replication. The present study investigated the effect of PEN110 treatment on the viability of protozoa in RBCs. STUDY DESIGN AND METHODS: B. microti-parasitized RBCs from infected hamsters were treated with PEN110 and inoculated to naïve animals. Parasitemia was detected by blood smears and PCR. Human RBCs infected with P. falciparum were treated with PEN110 and incubated with fresh RBCs. P. falciparum multiplication was detected by blood smears. Human RBCs spiked with T. cruzi and treated with PEN110 were analyzed for the presence of live parasites using in-vitro infectivity assay or by inoculating susceptible mice. RESULTS: Treatment of RBCs infected with B. microti or P. falciparum with 0.01 to 0.1 percent (vol/vol) PEN110 resulted in parasite inactivation to below the limit of detection during 24 hours. T. cruzi inoculated into human RBCs was inactivated below the limit of detection by 0.1 percent PEN110 after 3 hours. CONCLUSION: The study demonstrates that treatment of blood with PEN110 is highly effective in eradicating transfusion-transmitted protozoan parasites.