Infection by the nematode Angiostrongylus cantonensis induces differential expression of miRNAs in mouse brain

Ze Xun Mo, Jin Qiang Guo, Dan She, Xin Zhang, Santhosh Puthiyakunnon, Xiao Guang Chen, Zhong Dao Wu, Jyh Wei Shin, Li Wang Cui, Hua Li

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Background: The parasitic nematode Angiostrongylus cantonensis is the primary pathogen causing eosinophilic meningitis and meningoencephalitis in nonpermissive hosts. The larval parasites are eliminated by the host's immune responses in the central nervous system (CNS) through infiltration of eosinophils and lymphocytes. This study aimed to determine primary alterations of microRNA (miRNA) during A. cantonensis infection in mice. Methods: miRNA array was used to analyze the expression of miRNA in uninfected and A. cantonensis-infected mouse brains at 21 days postinfection (dpi). Target genes were predicted by miRDB software, and protein–protein interaction network was analyzed using STRING v9.1. Expression levels of selected miRNAs and cytokine production were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: Twenty-five mature miRNAs showed differential expression in infected mouse brains, of which 24 were upregulated and one was downregulated compared to the uninfected control. These 25 miRNAs were divided into five clusters, and the first upregulated cluster was selected for further bioinformatics analysis. Target gene prediction and gene ontology (GO) enrichment analysis revealed that the miRNAs were mainly related to the immune response. Furthermore, six target genes of mmu-miR-146a-5p were predicted to interact with tumor necrosis factor alpha (TNF-α). The in vitro study suggested that transfected mmu-miR-146a-5p inhibitor upregulated TNF-α and its target gene Traf6 in microglia following stimulation with A. cantonensis larval antigen. Conclusion: This study suggested a critical role of miRNAs in the host defense during A. cantonensis infection, providing new insights into the molecular mechanisms underlying the interaction between mmu-miR-146a-5p and TNF-α in angiostrongyliasis in nonpermissive hosts.

Original languageEnglish
Pages (from-to)94-102
Number of pages9
JournalJournal of Microbiology, Immunology and Infection
Volume51
Issue number1
DOIs
Publication statusPublished - 2018 Feb

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • General Immunology and Microbiology
  • Microbiology (medical)
  • Infectious Diseases

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