RESUMO
OBJECTIVES: Viral respiratory infections cause considerable morbidity and economic loss. While rhinoviruses (RV) typically cause little more than the common cold, they can produce severe infections and disease exacerbations in susceptible individuals, such as those with asthma. Variations in the regulation of key antiviral cytokines, particularly type I interferon (IFN-α and IFN-ß), may contribute to RV susceptibility. To understand this variability, we compared the transcriptomes of high and low type I IFN producers. METHODS: Blood mononuclear cells from 238 individuals with or without asthma were cultured in the presence or absence of RV. Those samples demonstrating high or low RV-stimulated IFN-α production (N = 75) underwent RNA-sequencing. RESULTS: Gene expression patterns were similar in samples from healthy participants and those with asthma. At baseline, the high IFN-α producer group showed higher expression of genes associated with plasmacytoid dendritic cells, the innate immune response and vitamin D activation, but lower expression of oxidative stress pathways than the low IFN-α producer group. After RV stimulation, the high IFN-α producer group showed higher expression of genes found in immune response biological pathways and lower expression of genes linked to developmental and catabolic processes when compared to the low IFN-α producer group. CONCLUSIONS: These differences suggest that the high IFN-α group has a higher level of immune system readiness, resulting in a more intense and perhaps more focussed pathogen-specific immune response. These results contribute to a better understanding of the variability in type I IFN production between individuals.
RESUMO
Viral respiratory infections are usually benign but can trigger asthma exacerbations. The factors associated with upper respiratory tract infection (cold) frequency are not fully understood, nor is it clear whether such factors differ between women and men.To determine which immunological and clinical variables associate with the frequency of self-reported respiratory infections (colds), 150 asthma cases and 151 controls were recruited. Associations between antiviral immune response variables: toll-like receptor (TLR)7/8 gene expression, plasmacytoid dendritic cell (pDC) numbers and interferon-α, tumour necrosis factor and interleukin-12 production, and asthma were then examined that might explain cold frequency.People with asthma cases reported more colds per year (median 3 versus 2; p<0.001) and had lower baseline TLR7 gene expression (odds ratio 0.12; p=0.02) than controls. Associations between many variables and cold frequency differed between women and men. In women, high blood neutrophil counts (ß=0.096, p=0.002), and younger age (ß=-0.017, p<0.001), but not exposure to children, were independently associated with more frequent colds. In men, low TLR7 expression (ß=-0.96, p=0.041) and high CLEC4C gene expression (a marker of pDC; ß=0.88, p=0.008) were independently associated with more frequent colds. Poor asthma symptom control was independently associated with reduced TLR8 gene expression (ß=-1.4, p=0.036) and high body mass index (ß=0.041, p=0.004).Asthma, age and markers of inflammation and antiviral immunity in peripheral blood are associated with frequent colds. Interestingly, the variables associated with cold frequency differed between women and men.
