Age-dependent innate responses to influenza A and B viruses in paediatric and adult primary nasal epithelial cells

Abstract

Introduction

Age is a major risk factor for influenza infection. The nasal epithelium is the early responder against infectious agents and environmental stimuli by controlling immune cell infiltration and releasing antimicrobial proteins. However, there is a lack of research distinguishing transcriptomic profiles across age upon influenza infection. While age-associated transcriptomic responses to respiratory viruses (e.g. SARS-CoV2, RSV) in lung have been reported, we, thus, hypothesised there are also age-dependent innate responses to influenza in nasal epithelial cells.

Material and Methods

In our study, primary human nasal epithelial cells (HNECs), obtained from healthy paediatric, adult, and elderly groups, were differentiated in air-liquid interface culture before being infected with influenza A and B. The RNA was extracted from cell lysates 48 hours post-infection for bulk RNA sequencing.

Results

Upon influenza A infection, there were 102, 682, and 627 upregulated and 0, 346, and 554 downregulated differentially expressed genes (DEGs) in the paediatric, adult and elderly groups, respectively. Among the upregulated genes, the three groups shared 86 common DEGs, while 320 common DEGs, enriched for more inflammatory and immune responses by cytokine production (e.g., IFN production, IL-17 signalling), were expressed in the adult and elderly groups. Strikingly, influenza A only induced downregulated DEGs in adult and elderly cells, which are associated with microtubule formation and ciliated function.

Fewer DEGs were induced upon influenza B infection, with only 69, 386, and 44 upregulations and 2, 13, and 2 downregulations in the paediatric, adult and elderly groups, respectively. Twenty-seven upregulated DEGs were commonly expressed amongst the three groups, while adults had 310 uniquely expressed DEGs, enriched for stronger immune defence responses against the virus and promoted more anti-viral cytokines (e.g., response to IL-1).

Discussion

Our analyses illuminate avenues for potential therapeutic approaches against influenza in different age groups, leveraging the power of in vitro experimentation.