IFN-α/IFN-λ responses to respiratory viruses in paediatric asthma

Abstract

We read with interest the paper by BERGAUER et al. [1] on innate immune responses to viral infection in paediatric asthma. The paper confirms previous reports on impaired interferon responses in stable asthma [2-4], but describes a hyperactive interferon production during asthma exacerbations associated with rhinovirus infection. The authors conclude that, despite impaired immune condition at stable state, the ability to upregulate type I interferons during the acute phase is preserved in asthmatic children. However, what is lacking from this study is the information on interferon production during acute rhinovirus infection in an age-matched group of non-asthmatics. Thus, how can it be conclusively excluded that the production of interferon is impaired during the rhinovirus-induced acute phase of asthma in the absence of such a comparative control group? A study which examined nasal washes of children during acute episodes of wheezing or rhinitis, reported lower levels of IFN-λ in children with wheezing than in those with acute rhinitis, even if the differences were not statistically significant [5]. The fact that asthmatic patients, once infected, have more severe manifestations of the infectious diseases [6] could possibly suggest an impaired response also in the acute phase, but conclusive data are lacking.

Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients

“…Our results suggest that IFN-β and IFN-λ production is altered during virus-induced exacerbations in asthmatic children. Compared to our study, the population differs from that of Bergauer et al by the age and also the severity of the exacerbation [11]. Furthermore, their results seems to be inconsistent on a larger cohort.…”

“…In the present study, patients infected with hRV appeared to display the same impairment (data not shown). In contrast, Bergauer et al recently reported that IFN-α levels were markedly increased in a small cohort of hRV-infected symptomatic asthmatic children (4.8 ± 0.64 years) as compared with infected but asymptomatic patients whereas IL-29 synthesis remains unchanged [11]. Our results suggest that IFN-β and IFN-λ production is altered during virus-induced exacerbations in asthmatic children.…”

“…hRV induce innate interferon (IFN) production in AEC via RIG-I, MDA5 and TLR3 [5,6] whereas influenza virus requires TLR7 [7]. Impairment in anti-viral response has been reported in asthmatic patients infected with hRV, as shown by altered production of type I IFNs (IFN-α/β) and/or type III IFNs [interleukin (IL)-28 and IL-29] [8][9][10][11]. However, if the deficient IFNs response has been reported in severe asthma, associated with a defect in TLR activation, it was not observed in well controlled asthma [12][13][14].…”

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness

“…28,32,47 The role of atopy is perplexing; Baraldo et al 34 showed that deficient interferon production was a feature of atopic asthmatic, nonatopic asthmatic, and nonasthmatic atopic children, 34 and studies focusing on allergic rhinitis without asthma have produced mixed results, 4,52 furthering the debate about whether it is asthma or atopy (or both) that drives this defect. Some argue that there is controversy regarding interferon deficiency in asthmatic patients because studies investigating interferon responses in patients with stable disease 53 or during AEs in vivo 54,55 find increased rather than decreased interferon levels in asthmatic patients. However, we would argue that studies of interferon levels in vivo will be confounded by differences in viral loads and that if one wishes to investigate the presence of interferon deficiency in a disease state, this can only be done by infecting cells with a standardized quantity of virus ex vivo or stimulating cells with a standard quantity of a viral mimic ex vivo.…”

Soluble ST2 regulation by rhinovirus and 25(OH)-vitamin D3 in the blood of asthmatic children

“…All methods in this study were performed in accordance with the relevant guidelines and regulations Two cohorts of preschool children (aged 4-6 years) with and without asthma were analysed. The recruitment of the subjects, inclusion and exclusion criteria, as well as the time-scale for clinical visits and data collection, have been described recently [24][25][26], and patient characteristics are reported in Table 1.…”