Modulation of host cell mechanics by Trypanosoma cruzi
β Scribed by Adam Mott; Guillaume Lenormand; Jaime Costales; Jeffrey J. Fredberg; Barbara A. Burleigh
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 237 KB
- Volume
- 218
- Category
- Article
- ISSN
- 0021-9541
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β¦ Synopsis
Abstract
To investigate the effects of Trypanosoma cruzi on the mechanical properties of infected host cells, cytoskeletal stiffness and remodeling dynamics were measured in parasiteβinfected fibroblasts. We find that cell stiffness decreases in a timeβdependent fashion in T. cruziβinfected human foreskin fibroblasts without a significant change in the dynamics of cytoskeletal remodeling. In contrast, cells exposed to T. cruzi secreted/released components become significantly stiffer within 2 h of exposure and exhibit increased remodeling dynamics. These findings represent the first direct mechanical data to suggest a physical picture in which an intact, stiff, and rapidly remodeling cytoskeleton facilitates early stages of T. cruzi invasion and parasite retention, followed by subsequent softening and disassembly of the cytoskeleton to accommodate intracellular replication of parasites. We further suggest that these changes occur through protein kinase A and inhibition of the Rho/Rho kinase signaling pathway. In the context of tissue infection, changes in host cell mechanics could adversely affect the function of the infected organs, and may play an important role on the pathophysiology of Chagas' disease. J. Cell. Physiol. 218: 315β322, 2009. Β© 2008 WileyβLiss, Inc.
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Chagas' disease, caused by Trypanosoma cruzi, is an urgent and highly prevalent danger that is endemic to Latin America, and which the research community continues to ignore. Each year, Chagas' disease kills more people in Latin America compared to any other parasite-borne disease, including malaria