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Ultrastructural Expansion Microscopy in Three In Vitro Life Cycle Stages of Trypanosoma cruzi
Published on: May 12, 2023
Host cytoplasmic processing bodies assembled by Trypanosoma cruzi during infection exert anti-parasitic activity
Eri Seto1, Yoko Onizuka2, Junko Nakajima-Shimada2
1Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Abstract:
Processing bodies (PBs) are cytoplasmic granules containing mRNAs and proteins involved in translation and degradation of mRNAs. PBs are constitutively present in cells and are induced to accumulate when external stressors including microbial infection are applied to cells, followed by a rapid translational arrest. We have examined the impact of Trypanosoma cruzi (T. cruzi, Tc) infection on host cytoplasmic PB assembly. Within 24h post-infection, we found the average number of PB foci per cell increased by more than 2-fold. Protein levels of PB components were unaltered during infection. These results indicated that Tc infection caused accumulation of PBs by changing the localization pattern of PB protein components. To elucidate the role of the accumulated PBs on Tc infection, we knocked down PBs using a siRNA specific for PB components EDC4 and Lsm14A, which are involved in mRNA decapping and translational repression, respectively. We observed that the inhibition of PB accumulation significantly enhanced the infectivity and growth of intracellular amastigotes. Depletion of PBs did not affect nitric oxide (NO) production during Tc infection, indicating that the growth promotion was not caused by modulation of NO-mediated killing of Tc. Our results suggest that the accumulated PBs partially contribute to anti-parasitic responses by manipulating the host's mRNA metabolism.
Insights
Trypanosoma cruzi infection causes host cells to accumulate processing bodies (PBs). Inhibiting PB formation enhances parasite growth, suggesting PBs play a role in anti-parasitic defense.
Area of Science:
- Cell Biology
- Parasitology
- Immunology
Background:
- Processing bodies (PBs) are cellular granules crucial for mRNA regulation.
- PBs accumulate under stress, including microbial infections, leading to translational arrest.
Purpose of the Study:
- To investigate the impact of Trypanosoma cruzi (T. cruzi) infection on host cytoplasmic PB assembly.
- To determine the role of T. cruzi-induced PB accumulation in host-parasite interactions.
Main Methods:
- Quantified PB foci in T. cruzi-infected cells.
- Utilized siRNA to knock down PB components (EDC4, Lsm14A).
- Assessed T. cruzi infectivity and intracellular amastigote growth.
- Measured nitric oxide (NO) production.
Main Results:
- T. cruzi infection increased PB foci by over 2-fold within 24 hours.
- PB component protein levels remained unchanged.
- Knocking down PBs significantly enhanced T. cruzi infectivity and amastigote growth.
- PB depletion did not alter NO production.
Conclusions:
- T. cruzi infection induces host PB accumulation by altering protein localization.
- Accumulated PBs contribute to anti-parasitic responses by modulating host mRNA metabolism.
- PBs partially restrict T. cruzi growth independently of nitric oxide production.
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