Dataset Information

Age-associated Changes in the Respiratory Epithelial Response to Influenza Infection [hNEC]

ABSTRACT: This study evaluates how aging impacts the interaction between influenza viruses and human respiratory epithelial cells. Our results indicate that aging is associated with a decrease in the gene expression of key antiviral mediators, IFITM1 and MX1, and a decrease in the expression of MHC-I and TAP mRNA and proteins responsible for antigen processing and presentation. Importantly however epithelial cells from older individuals produce similar, and in some cases greater, levels of chemokines as compared with hNECs from younger individuals. Taken together a defect in antigen processing and presentation could result in impaired clearance of infected epithelial cells allowing them to continue to produce inflammatory cytokines and chemokines resulting in prolonged inflammation and perhaps increased severity of disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE89880 | GEO | 2016/11/16

SECONDARY ACCESSION(S): PRJNA353638

REPOSITORIES: GEO

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Project description:E2 exposure significantly decreased peak viral titer in hNECs from female donors. We used microarray analyses to identify global gene expression patterns between E2 and vehicle exposed hNECs from female donors Influenza causes an acute infection characterized by virus replication in respiratory epithelial cells. The severity of influenza and other respiratory diseases changes over the life course and during pregnancy in women, suggesting that sex steroid hormones, such as estrogens, may be involved. Using primary, differentiated human nasal epithelial cell (hNEC) cultures from adult male and female donors, we exposed cultures to the endogenous 17Î²-estradiol (E2) or select estrogen receptor modulators (SERMs), then infected cultures with a seasonal influenza A virus (IAV) to determine whether estrogenic signaling could affect the outcome of IAV infection and whether these effects where sex-dependent. Estradiol, raloxifene, and bisphenol A decreased IAV titers in hNECs from female, but not male, donors. The estrogenic decrease in viral titer was dependent on the genomic estrogen receptor- 2 (ESR2) as neither genomic ESR1 nor non- genomic GPR30 were expressed in hNEC cultures and addition of the genomic ER antagonist ICI 182,780 reversed the antiviral effects of E2. Treatment of hNECs with E2 had no effect on interferon or chemokine secretion, but significantly downregulated cell metabolic processes, including genes that encode for zinc finger proteins, many of which contain estrogen response elements in their promoters. These data provide novel insights into the cellular and molecular mechanisms of how natural and synthetic estrogens impact IAV infection in respiratory epithelial cells derived from humans. Primary human nasal epithelial cells from females were exposed to E2 for 24h prior to infection, then infected with an H3N2 strain of influenza a virus for 2 hours. At 24 and 48h post infection, hNECs were collected in Trizol for RNA extraction and hybridization on Affymetrix Human Gene ST 2.0 microarrays.

Dataset Information

Age-associated Changes in the Respiratory Epithelial Response to Influenza Infection [hNEC]

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