Dataset Information

Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression.

ABSTRACT:

Background

Eosinophils in asthmatic airways are associated with risk of exacerbations. The most common cause of asthma exacerbations is viral respiratory infections, particularly human rhinovirus (HRV).

Objective

To determine the mechanism by which eosinophils may influence virus-induced responses.

Methods

We used an in vitro coculture model of primary human eosinophils and the BEAS-2B epithelial cell line either stimulated with HRV1A infection or polyinosinic-polycytidylic acid (poly[I:C]). The messenger RNA (mRNA) expression of interferon (IFN) ?1 and IFN-?1 was assessed by quantitative reverse-transcriptase polymerase chain reaction and the protein level of IFN- ?1 by enzyme-linked immunosorbent assay.

Results

Both poly(I:C) and HRV1A infection induced BEAS-2B expression of IFN-?1 and IFN-?1 mRNA. Coculture of eosinophils resulted in suppression of poly(I:C)-stimulated IFN-?1 and IFN-?1 mRNA expression (2.5-fold and 3.6-fold less, respectively). Separation of cells did not block eosinophil regulatory activity. Coculture of eosinophils with HRV1A-infected BEAS-2B cells also suppressed IFN-?1 and IFN-?1 mRNA (5.7-fold and 5.0-fold less, respectively) and reduced IFN-?1 protein secretion (1.6-fold decrease). This corresponded to a 34% increase in the quantity of HRV1A virus RNA on coculture with eosinophils. Recombinant transforming growth factor ? suppressed IFN-?1 from HRV1A-infected BEAS-2B cells. Coculture of eosinophils and BEAS-2B cells induced transforming growth factor ? secretion, which may mediate suppression of HRV-induced interferon expression.

Conclusion

Eosinophils suppressed HRV-induced expression of interferons from epithelial cells, resulting in increased quantity of HRV. This represents one mechanism for interaction between allergic inflammation and innate immunity.

SUBMITTER: Mathur SK

PROVIDER: S-EPMC3708694 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression.

Mathur Sameer K SK Fichtinger Paul S PS Kelly John T JT Lee Wai-Ming WM Gern James E JE Jarjour Nizar N NN

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 20130701 1

<h4>Background</h4>Eosinophils in asthmatic airways are associated with risk of exacerbations. The most common cause of asthma exacerbations is viral respiratory infections, particularly human rhinovirus (HRV).<h4>Objective</h4>To determine the mechanism by which eosinophils may influence virus-induced responses.<h4>Methods</h4>We used an in vitro coculture model of primary human eosinophils and the BEAS-2B epithelial cell line either stimulated with HRV1A infection or polyinosinic-polycytidylic ...[more]

PMID: 23806456

Similar Datasets

Project description:Influenza A virus (IAV) is an airborne pathogen that causes significant morbidity and mortality each year. Macrophages (Mϕ) are the first immune population to encounter IAV virions in the lungs and are required to control infection. In the present study, we explored the mechanism by which cytokine signaling regulates the phenotype and function of Mϕ via epigenetic modification of chromatin. We have found that type I interferon (IFN-I) potently upregulates the lysine methyltransferase Setdb2 in murine and human Mϕ, and in turn Setdb2 regulates Mϕ-mediated immunity in response to IAV. The induction of Setdb2 by IFN-I was significantly impaired upon inhibition of the JAK-STAT signaling cascade, and chromatin immunoprecipitation revealed that both STAT1 and interferon regulatory factor 7 bind upstream of the transcription start site to induce expression. The generation of Setdb2LacZ reporter mice revealed that IAV infection results in systemic upregulation of Setdb2 in myeloid cells. In the lungs, alveolar Mϕ expressed the highest level of Setdb2, with greater than 70% lacZ positive on day 4 post-infection. Silencing Setdb2 activity in Mϕ in vivo enhanced survival in lethal IAV infection. Enhanced host protection correlated with an amplified antiviral response and less obstruction to the airways. By tri-methylating H3K9, Setdb2 silenced the transcription of Mx1 and Isg15, antiviral effectors that inhibit IAV replication. Accordingly, a reduced viral load in knockout mice on day 8 post-infection was linked to elevated Isg15 and Mx1 transcript in the lungs. In addition, Setdb2 suppressed the expression of a large number of other genes with proinflammatory or immunomodulatory function. This included Ccl2, a chemokine that signals through CCR2 to regulate monocyte recruitment to infectious sites. Consistently, knockout mice produced more CCL2 upon IAV infection and this correlated with a 2-fold increase in the number of inflammatory monocytes and alveolar Mϕ in the lungs. Finally, Setdb2 expression by Mϕ suppressed IL-2, IL-10, and IFN-γ production by CD4+ T cells in vitro, as well as proliferation in IAV-infected lungs. Collectively, these findings identify Setdb2 as a novel regulator of the immune system in acute respiratory viral infection.

Dataset Information

Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression.

Background

Objective

Methods

Results

Conclusion

Publications

Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets