NMP4 regulates the innate immune response to influenza A virus infection.

Mucosal Immunology
Shuangshuang YangBaohua Zhou

Abstract

Severe influenza A virus infection typically triggers excessive and detrimental lung inflammation with massive cell infiltration and hyper-production of cytokines and chemokines. We identified a novel function for nuclear matrix protein 4 (NMP4), a zinc-finger-containing transcription factor playing roles in bone formation and spermatogenesis, in regulating antiviral immune response and immunopathology. Nmp4-deficient mice are protected from H1N1 influenza infection, losing only 5% body weight compared to a 20% weight loss in wild type mice. While having no effects on viral clearance or CD8/CD4 T cell or humoral responses, deficiency of Nmp4 in either lung structural cells or hematopoietic cells significantly reduces the recruitment of monocytes and neutrophils to the lungs. Consistent with fewer innate cells in the airways, influenza-infected Nmp4-deficient mice have significantly decreased expression of chemokine genes Ccl2, Ccl7 and Cxcl1 as well as pro-inflammatory cytokine genes Il1b and Il6. Furthermore, NMP4 binds to the promoters and/or conserved non-coding sequences of the chemokine genes and regulates their expression in mouse lung epithelial cells and macrophages. Our data suggest that NMP4 functions to promote monoc...Continue Reading

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Citations

Aug 22, 2021·Calcified Tissue International·Joseph BidwellCarmella Evans-Molina

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Methods Mentioned

BETA
bronchoalveolar lavage
flow cytometry
PMA
ELISA
PCR
ChIP
FACS
transfection

Software Mentioned

GraphPad
IDT
Prism

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