Temporal Nasal Epithelial Gene Expression Patterns in Healthy Individuals Infected with Rhinovirus-16, and Its Modulation by Carrot Rhamnogalacturonan-I

Innate immune and interferon-induced responses to in vivo nasal infection with rhinovirus (RV)16 in healthy subjects are accelerated by low-dose dietary supplementation with carrot-derived pectic polysaccharide rhamnogalacturonan-I (cRG-I), together with reduced duration and severity of symptoms. We aimed to further identify temporal mRNA responses by nasal epithelial cells (NEC) after RV16 infection, and to assess the effect of cRG-I supplementation. NECs were obtained prior to (day(d)-55) and after 8-weeks (d-1) of supplementation (0, 0.3, 1.5 g/d), and on d3, d6, d9 and d13 after exposure to 100 TCID50 RV16. Transcriptome data were generated and analysed with the R2: Genomics Analysis and Visualization platform (https://r2.amc.nl). RV16 infection reduced expression of genes related to oxidative phosphorylation (d3), induced gene expression by interferon (d6-9), and reduced expression of cilia-related genes (d13). cRG-I changed these responses. At low-dose, gene expression of important transcription factors and effector molecules (IRF4, IRF8, RFX3, IL-1B, CASP1) was enhanced markedly earlier (d3-6). At high-dose, cRG-I induced expression of inflammasome-related genes already after 8-weeks supplementation. cRG-I, in a dose-dependent manner, significantly affected the sequence and intensity of genes that regulate pathways involved in anti-viral responses and epithelial repair. This may underlie the reduced duration and severity of symptoms.