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Published on: September 30, 2017
Attachment of Trypanosoma cruzi trypomastigotes to receptors at restricted cell surface domains
S Schenkman1, C Diaz, V Nussenzweig
1Department of Pathology, New York University Medical Center, New York 10016.
Abstract:
We have used glutaraldehyde-fixed target cells to study the attachment phase of cell invasion by live trypomastigotes of Trypanosoma cruzi, and determined that attachment is polarized and receptor-mediated. T. cruzi trypomastigotes bind much less efficiently to confluent epithelial cells, which are polarized, than to sparse epithelial cells. When the tight junctions of confluent epithelial cells are disrupted by removing Ca2+ from the incubation medium before glutaraldehyde fixation, binding of T. cruzi increases. T. cruzi also shows preference for attachment underneath cells or to the edges of cells. The binding occurs within a few minutes, is saturable, and is influenced by the parasite developmental stage. Fab fragment derived from monoclonal antibodies that immunoprecipitate a 160-kDa molecule present only on the surface of trypomastigotes inhibit adhesion to fixed and live cells. Future characterization of the target cell receptors for this molecule and the use of fixed target cells should facilitate studies of the mechanisms involved in the initial interaction of T. cruzi with its host cells.
Insights
Trypanosoma cruzi attachment to host cells is polarized and receptor-mediated. This interaction, crucial for cell invasion, is influenced by cell density and parasite stage, involving a specific 160-kDa trypomastigote surface molecule.
Area of Science:
- Parasitology
- Cell Biology
- Infectious Diseases
Background:
- Trypanosoma cruzi (T. cruzi) is a protozoan parasite responsible for Chagas disease.
- Understanding the initial host cell invasion mechanisms is critical for developing therapeutic strategies.
Purpose of the Study:
- To investigate the attachment phase of T. cruzi trypomastigote invasion.
- To determine if attachment is polarized and receptor-mediated.
Main Methods:
- Utilized glutaraldehyde-fixed target cells to study T. cruzi attachment.
- Assessed binding efficiency to confluent versus sparse epithelial cells.
- Investigated the effect of calcium (Ca2+) on cell junction integrity and parasite binding.
- Employed Fab fragments from monoclonal antibodies targeting a 160-kDa trypomastigote surface molecule.
Main Results:
- T. cruzi attachment is polarized and receptor-mediated.
- Binding is less efficient to confluent, polarized epithelial cells compared to sparse cells.
- Disrupting epithelial tight junctions with Ca2+ removal increased T. cruzi binding.
- Parasite binding occurred rapidly, was saturable, and varied with developmental stage.
- Inhibition of a 160-kDa surface molecule on trypomastigotes reduced adhesion.
Conclusions:
- The 160-kDa surface molecule on T. cruzi trypomastigotes plays a key role in host cell attachment.
- Fixed target cells are a valuable tool for studying T. cruzi-host cell interactions.
- Further characterization of target cell receptors will elucidate T. cruzi invasion mechanisms.
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