NMP4 regulates the innate immune response to influenza A virus infection

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Severe influenza A virus infection causes detrimental lung inflammation.
• Nuclear matrix protein 4 (NMP4) is a transcription factor with known roles in bone and sperm development.
• The role of NMP4 in antiviral immunity and influenza pathogenesis is unknown.

Purpose of the Study:

• To investigate the function of NMP4 in regulating the immune response to influenza A virus infection.
• To determine the impact of NMP4 deficiency on influenza-induced lung immunopathology.

Main Methods:

• Utilized Nmp4-deficient mice and wild-type controls infected with H1N1 influenza A virus.
• Assessed viral clearance, T cell responses, and innate immune cell infiltration (monocytes, neutrophils) in the lungs.
• Measured expression of chemokine and pro-inflammatory cytokine genes.
• Investigated NMP4 binding to gene regulatory regions in lung epithelial cells and macrophages.

Main Results:

• Nmp4-deficient mice exhibited significantly reduced body weight loss (5%) compared to wild-type mice (20%) after H1N1 infection.
• NMP4 deficiency did not affect viral clearance or adaptive immune responses (T cells, humoral immunity).
• Absence of NMP4 markedly reduced monocyte and neutrophil recruitment to the lungs, decreasing expression of Ccl2, Ccl7, Cxcl1, Il1b, and Il6.
• NMP4 directly binds to regulatory elements of chemokine genes, controlling their expression.

Conclusions:

• NMP4 promotes excessive innate immune cell recruitment and lung inflammation during influenza A infection.
• NMP4 functions by upregulating monocyte- and neutrophil-attracting chemokines.
• Targeting NMP4 may offer a therapeutic strategy to mitigate influenza-induced lung immunopathology.