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Physiol Genomics. 2018 May 1;50(5):299-312. doi: 10.1152/physiolgenomics.00122.2017. Epub 2018 Mar 9.

Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

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Departments of Pediatrics and Communicable Diseases, University of Michigan Medical School , Ann Arbor, Michigan.
Department of Epidemiology, University of Michigan School of Public Health , Ann Arbor, MI.
Department of Molecular and Integrative Physiology, University of Michigan Medical School , Ann Arbor, Michigan.


Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.


AGO; CCL8; CXCL10; GSDMD; IFN-γ; IL-6; TNFSF10; VNN1; asthma; gene expression

[Available on 2019-05-01]
[Indexed for MEDLINE]

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