Trypanosoma cruzi assembles host cytoplasmic processing bodies to evade the innate immune response

Processing bodies (P-bodies, PBs) are cytoplasmic foci formed by condensation of translationally inactivated messenger ribonucleoprotein particles (mRNPs). Infection with the protozoan parasite Trypanosoma cruzi (T. cruzi) promotes PB accumulation in host cells, suggesting their involvement in host mRNA metabolism during parasite infection. To identify PB-regulated mRNA targets during T. cruzi infection, we established a PB-defective human fibrosarcoma cell line by knocking out the enhancer of mRNA decapping 4 (EDC4), an essential component of PB assembly. Next-generation sequencing was used to establish transcriptome profiles for wild-type (WT) and EDC4 knockout (KO) cells infected with T. cruzi for 0, 3, and 24 h. Ingenuity pathway analysis based on the differentially expressed genes revealed that PB depletion increased the activation of several signaling pathways involved in the innate immune response. The proinflammatory cytokine IL-1β was significantly upregulated following infection of PB-deficient KO cells, but not in WT cells, at the mRNA and protein levels. Furthermore, the rescue of PB assembly in KO cells by GFP-tagged wild-type EDC4 (+WT) suppressed IL-1β expression, whereas KO cells with the C-terminal-deleted mutant EDC4 (+Δ) failed to rescue PB assembly and downregulate IL-1β production. Our results suggest that T. cruzi assembles host PBs to counteract antiparasitic innate immunity. [Display omitted] •Processing bodies (PBs) are cytoplasmic mRNA granules involved in mRNA metabolism.•Host PB assembly is facilitated by Trypanosoma cruzi during early infection.•T.cruzi-responsive innate immune genes and pathways are downregulated by PBs.•PB assembly is critical for the suppression of IL-1β by T. cruzi.•PBs are likely to be exploited by T. cruzi for immune evasion.