title: Infection by the nematode Angiostrongylus cantonensis induces differential expression of miRNAs in mouse brain.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathogen Biology and Experimental Teaching Centre of Preventive Medicine, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Key Laboratory for Tropical Disease Research of Guangdong Province, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Ze-Xun
authors.initials: ZX
authors.lastname: Mo
authors.affiliation: Department of Pathogen Biology and Experimental Teaching Centre of Preventive Medicine, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Key Laboratory for Tropical Disease Research of Guangdong Province, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Jin-Qiang
authors.initials: JQ
authors.lastname: Guo
authors.affiliation: Department of Pathogen Biology and Experimental Teaching Centre of Preventive Medicine, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Key Laboratory for Tropical Disease Research of Guangdong Province, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: She
authors.affiliation: Department of Pathogen Biology and Experimental Teaching Centre of Preventive Medicine, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Key Laboratory for Tropical Disease Research of Guangdong Province, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathogen Biology and Experimental Teaching Centre of Preventive Medicine, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Key Laboratory for Tropical Disease Research of Guangdong Province, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Santhosh
authors.initials: S
authors.lastname: Puthiyakunnon
authors.affiliation: Department of Pathogen Biology and Experimental Teaching Centre of Preventive Medicine, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Key Laboratory for Tropical Disease Research of Guangdong Province, School of Public Health, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Chen
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, China.
authors.forename: Zhong-Dao
authors.initials: ZD
authors.lastname: Wu
authors.affiliation: Department of Parasitology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Jyh-Wei
authors.initials: JW
authors.lastname: Shin
authors.affiliation: Department of Entomology, Pennsylvania State University, 501 ASI Building, University Park, PA 16802, USA.
authors.forename: Li-Wang
authors.initials: LW
authors.lastname: Cui
authors.affiliation: Department of Pathogen Biology and Experimental Teaching Centre of Preventive Medicine, Key Laboratory of Prevention and Control for Emerging Infectious Diseases of Guangdong Higher Institutes, Key Laboratory for Tropical Disease Research of Guangdong Province, School of Public Health, Southern Medical University, Guangzhou, China. Electronic address: lih@smu.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
mesh_terms: D056704:Adaptive Immunity; D017185:Angiostrongylus cantonensis / Q000276:immunology* / Q000472:pathogenicity*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000469:parasitology*; D002490:Central Nervous System / Q000276:immunology / Q000469:parasitology; D016000:Cluster Analysis; D019295:Computational Biology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D006790:Host-Parasite Interactions / Q000276:immunology; D007814:Larva / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D017628:Microglia; D054730:Protein Interaction Domains and Motifs; D060888:Real-Time Polymerase Chain Reaction; D017206:Strongylida Infections / Q000276:immunology / Q000469:parasitology; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha
keywords: Angiostrongylus cantonensis; TNF-α; immune response; microRNAs; mmu-miR-146a-5p