Related Experiment Video
Updated: Jul 31, 2026
Optimized Protocol for Efficient Transfection of Dendritic Cells without Cell Maturation
Published on: July 8, 2011
MiR674 inhibits the neuraminidase-stimulated immune response on dendritic cells via down-regulated Mbnl3
Jian Lin1, Ya T Chen1, Jing Xia1
1Life Science College, Nanjing Agricultural University, Weigang, Nanjing, Jiangsu, PR China.
Abstract:
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.
Insights
Avian influenza virus neuraminidase (NA) enhances dendritic cell (DC) maturation and immune responses by upregulating specific microRNAs. Inhibiting these microRNAs blocks NA-induced DC maturation, revealing a novel mechanism for influenza virus immune evasion.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Neuraminidase (NA) from H9N2 avian influenza virus (AIV) aids viral entry by cleaving sialic acid.
- Dendritic cells (DCs) are key antigen-presenting cells regulated by microRNAs (miRNAs).
- Understanding miRNA-mediated immune repression in DCs is crucial for influenza AIV research.
Purpose of the Study:
- Investigate the molecular mechanisms of miRNA-induced immune repression in mouse DCs by H9N2 AIV neuraminidase.
- Identify specific miRNAs regulated by NA and their impact on DC function.
- Elucidate the role of NA-induced miRNAs in modulating DC maturation and immune activation.
Main Methods:
- Screening and verification of miRNAs induced by NA in mouse DCs.
- Analysis of DC surface markers (CD80, MHCII) and lymphocyte activation assays.
- Overexpression and inhibition of specific miRNAs (miR-155, miR-674) to assess their role in DC maturation.
- Prediction and experimental validation of miRNA target genes.
Main Results:
- H9N2 AIV NA up-regulated miR-155, miR-674, and miR-499, while down-regulating miR-181b1 in DCs.
- NA significantly increased DC surface markers (CD80, MHCII) and enhanced lymphocyte activation compared to other viral proteins.
- Overexpression of miR-155 and miR-674 promoted DC maturation; inhibiting them blocked NA-induced maturation.
- Mbnl3 was identified as a key target gene of miR-674, crucial for DC maturation.
Conclusions:
- H9N2 AIV NA promotes DC maturation and immune activation through specific miRNA regulation, notably miR-155 and miR-674.
- NA utilizes miR-674 to target genes like Mbnl3, thereby modulating DC maturation.
- These findings reveal a novel mechanism of immune evasion by influenza viruses involving miRNA-mediated repression of DC function, offering potential targets for antiviral prophylaxis.
Related Concept Videos
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:25Inhibitors Of Virion Release