Ze-Xun Mo1, Jin-Qiang Guo1, Dan She1, Xin Zhang1, Santhosh Puthiyakunnon1, Xiao-Guang Chen1, Zhong-Dao Wu2, Jyh-Wei Shin3, Li-Wang Cui4, Hua Li5. 1. 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. 2. Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, Guangdong Province, China. 3. Department of Parasitology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan. 4. Department of Entomology, Pennsylvania State University, 501 ASI Building, University Park, PA 16802, USA. 5. 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.
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.
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-infectedmouse 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 tumornecrosis 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.
Authors: Renzo Gutierrez-Loli; Miguel A Orrego; Oscar G Sevillano-Quispe; Luis Herrera-Arrasco; Cristina Guerra-Giraldez Journal: Front Microbiol Date: 2017-09-29 Impact factor: 5.640