Host cytoplasmic processing bodies assembled by Trypanosoma cruzi during infection exert anti-parasitic activity

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.

Keywords: Processing body; Trypanosoma cruzi; mRNA metabolism.