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Critical role of pDC in regulating gene expression and innate immune responses to human rhinovirus

ABSTRACT: Human rhinoviruses (HRV) are usually innocuous viruses; however, they can trigger serious consequences in certain individuals, especially in the setting of deficient interferon (IFN) synthesis. Plasmacytoid dendritic cells (pDC) are key IFN producing cells, though we know little about the mechanisms by which pDC regulate HRV-induced immune responses. Herein we used gene expression microarrays to examine HRV-induced mRNA in blood mononuclear cells from healthy people, in combination with pDC depletion to assess whether observed expression patterns were pDC dependent. As expected, pDC depletion led to a major reduction in HRV-induced IFN-α release, and this was associated with profound differences in gene expression between intact PBMC and pDC depleted PBMC. pDC depletion led to major changes in upstream regulators, with 70-80% of the HRV activated genes appearing to be pDC dependent. PCR validation experiments confirmed changes seen in the microarrays, specifically the extent to which the following differentially expressed genes were highly pDC dependent: the transcription factor IRF7, both IL-27 chains (IL-27 and EBI3), the alpha chain of the IL-15 receptor (IL-15RA) and the IFN stimulated gene IFI27. IL-6, IFN-γ and IL-27 protein synthesis were also highly pDC dependent. Supplementing pDC-depleted cultures with either recombinant IFN-γ, IL-15, IL-27 or IL-6 was able to restore the IFN-α response, thereby compensating for the absence of pDC. Though pDC comprise only a minority population of migratory leukocytes, our findings highlight the extent to which these cells are able to exert a profound effect on the immune response to HRV.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99858 | GEO | 2017/06/10

SECONDARY ACCESSION(S): PRJNA389790

REPOSITORIES: GEO

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Major and Minor Group Human Rhinovirus Response in Human Macrophages

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