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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE89882 | GEO | 2016/11/16

SECONDARY ACCESSION(S): PRJNA353636

REPOSITORIES: GEO

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Age-Associated Changes in the Respiratory Epithelial Response to Influenza Infection.

Project description:Older adults suffer a disproportionate burden of influenza-related morbidity and mortality typically attributed to defects in the aging immune system collectively known as immunosenescence. While the age-related decline in the adaptive immune system has been well characterized, little is known about how aging affects the principal site of influenza infection-the nasal epithelium. In human nasal epithelial cell cultures (hNECs) from older adults, we found similar or increased levels of cytokines during influenza infection compared with hNECs from younger individuals. However, hNECs from older individuals demonstrated decreased mRNA expression for several key proteins that affect clearance of infected cells, including MHC-I and transporter associated with antigen presentation (TAP). These findings were confirmed at the level of protein expression. In vivo studies corroborated the in vitro differences in MHC-I and TAP gene expression and also revealed important decreases in the expression of key influenza-specific antiviral mediators MX1 and IFITM1. Furthermore, epithelial cell-cytotoxic T lymphocyte co-cultures demonstrate that CTL cytotoxic activity is dose-dependent on MHC-I antigen presentation. Taken together, these results indicate that aging is associated with important changes in the nasal epithelium, including antigen presentation and antiviral pathways, which may contribute to increased severity of disease in older adults through impaired clearance of infected cells.

| S-EPMC6230210 | biostudies-literature

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

Project description: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.

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

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

Project description:Age-associated Changes in the Respiratory Epithelial Response to Influenza Infection

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