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

Autor: Seto E; Education and Research Support Center, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Electronic address: eri.seto@gunma-u.ac.jp., Kina S; Center for Medical Education, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan., Kawabata-Iwakawa R; Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan., Suzuki M; Department of Molecular and Cellular Parasitology, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan., Onizuka Y; Department of Molecular and Cellular Parasitology, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan., Nakajima-Shimada J; Department of Molecular and Cellular Parasitology, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2024 Nov; Vol. 1868 (11), pp. 130686. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1016/j.bbagen.2024.130686
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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