Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy

Abstract

BackgroundAirway epithelial cells (AEC) from patients with asthma, appear to have an impaired interferon (IFN)-β and -λ response to infection with rhinovirus.ObjectivesTo determine if impaired IFN responses can be identified in young children at risk of developing asthma due to atopy and/or early life wheeze, and if the site of infection or the infecting virus influence the antiviral response.MethodsNasal (N) and tracheal (T) epithelial cells (EC) were collected from children categorised with atopy and/or wheeze based on specific IgE to locally common aeroallergens and a questionnaire concerning respiratory health. Submerged primary cultures were infected with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV), and IFN production, inflammatory cytokine expression and viral replication quantified.ResultsNasal epithelial cells (NEC), but not tracheal epithelial cells (TEC), from children with wheeze and/or atopy produced less IFN-β, but not IFN-λ, in response to RSV infection; this was associated with higher viral shedding. However, IFN-regulated factors IRF-7, Mx-1 and CXCL-10, and inflammatory cytokines were not differentially regulated. NECs and TECs from children with wheeze and/or atopy demonstrated no impairment of the IFN response (β or λ) to hMPV infection. Despite this, more hMPV was shed from these cells.ConclusionsAECs from children with wheeze and/or atopy do not have an intrinsic defect in the production of IFN-β or -λ, however, this response is influenced by the infecting virus. Higher viral load is associated with atopy and wheeze suggesting an impaired antiviral response to RSV and hMPV that is not influenced by production of IFNs.

Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment

“…In contrast, there is not an increase in susceptibility to infection or replication by RSV in adult asthmatics compared to healthy controls (174). However, those at greatest risk of developing asthma, children with wheeze and atopy, experience significantly elevated RSV load compared to healthy children (175). Expression of antiviral immune factors from bronchial epithelium was largely intact as reported in both studies (174,175).…”

“…However, those at greatest risk of developing asthma, children with wheeze and atopy, experience significantly elevated RSV load compared to healthy children (175). Expression of antiviral immune factors from bronchial epithelium was largely intact as reported in both studies (174,175). Interestingly, RSV uses entry receptors, TLR4 and CX3CR1 (discussed in the section above), that are upregulated during airway inflammation in both asthma and COPD.…”

Novel concepts in airway inflammation and remodelling in asthma

“…In addition, bronchial epithelial cell function is altered in pre-school wheezers [66], and although it is uncertain whether this predicts progression to asthma, given the evidence of abnormal epithelial function in children and adults with established asthma [67], and the identification of genes associated with asthma being expressed in the bronchial epithelium [68,69], this is definitely an important cell that should be further investigated as a target for disease modification. A further advantage is its direct accessibility via the inhaled route.…”

Alzheimer’s Disease of the Immune System: A New Variant of Immune Deficiency

“…Downregulation of TLRs may be responsible for increased susceptibility of asthmatics to mycoplasma infection, as mycoplasma clearance in an allergic mouse model has been demonstrated to be due to TLR2 down-regulation [32]. Another viral/ immune example that may be related to the role of atopy is RSV [33].…”