MiR674 inhibits the neuraminidase-stimulated immune response on dendritic cells via down-regulated Mbnl3.
Neuraminidase (NA), a structural protein of the H9N2 avian influenza virus (H9N2 AIV), can facilitate viral invasion of the upper airway by cleaving the sialic acid moieties on mucin. Dendritic cells (DCs) are major antigen-presenting cells whose immune functions, such as presenting antigens and activating lymphocytes, can be regulated by microRNAs. Here, we studied the molecular mechanism of miRNA-induced repression of immune responses in mouse DCs. First, we screened for and verified the miRNAs induced by NA. Then, we showed that, consistent with the H9N2 virus treatment, the viral NA up-regulated the expression of miR-155, miR-674, and miR-499 in DCs; however, unlike H9N2 virus treatment, the presence of NA was associated with reduced expression of miR-181b1. Our results suggest that NA significantly increased DC surface markers CD80 and MHCII and enhanced the ability of activating lymphocytes and secreting cytokines compared with HA, NP and M2. Meanwhile, we found that miR-674 and miR-155 over-expression increased all surface markers of DC. Nevertheless, by inhibiting the expression of miR-674 and miR-155, NA lost the ability to promote DC maturation. Furthermore, we predicted and demonstrated that Pgm2l1, Aldh18a1, Camk1d, and Mbnl3 were the target genes of miR-674. Among them, Mbnl3 interference strongly blocked the mature DCs. Collectively, our data shed new light on the roles of and mechanisms involved in the repression of DCs by miRNAs, which may contribute to efforts to develop a prophylaxis for the influenza virus.
Life Science College, Nanjing Agricultural University, Weigang, Nanjing, Jiangsu, PR China.
Jian
J
Lin
Life Science College, Nanjing Agricultural University, Weigang, Nanjing, Jiangsu, PR China.
Ya T
YT
Chen
Life Science College, Nanjing Agricultural University, Weigang, Nanjing, Jiangsu, PR China.
Jing
J
Xia
College of Veterinary Medicine, Nanjing Agricultural University, Weigang, Jiangsu, PR China.
Qian
Q
Yang
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D007107:Immune System; D053127:Influenza A Virus, H9N2 Subtype; D016086:Lentivirus; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins
D002352:Carrier Proteins; D016207:Cytokines; C522920:MBNL3 protein, mouse; C000613947:MIRN674 microRNA, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016601:RNA-Binding Proteins; D009439:Neuraminidase
Immune response; Immunity; Immunology and Microbiology Section; dendritic cells; immune regulation; miR-674; neuraminidase; virus replication