Children With Asthma Have Impaired Innate Immunity and Increased Numbers of Type 2 Innate Lymphoid Cells Compared With Healthy Controls

Abstract

Background: Asthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children.

Objective: The present study aimed to evaluate cytokine responses of peripheral blood mononuclear cells (PBMCs), PBMC composition and lung function in children with and without asthma.

Methods: Using a case-control design, we compared 48 children with asthma aged 3-11 years with 14 age-matched healthy controls. PBMC composition and cytokine production including interferon (IFN)-γ, interleukin (IL)-1β, IL-5 and lL-6 following stimulation with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS) were measured. Lung function was assessed using impulse oscillometry and nitrogen multiple breath washout.

Results: The frequency of group 2 innate lymphoid cells were significantly higher in asthmatics and PBMCs from asthmatics had deficient IFN-γ production in response to both RV1B and LPS compared with controls (P<0.01). RV1B-induced IL-1β response and HDM-stimulated IL-5 production was higher in asthmatics than controls (P<0.05). In contrast, IL-1β and IL-6 were significantly reduced in response to HDM and LPS in asthmatics compared to controls (P<0.05). Children with asthma also had reduced pulmonary function, indicated by lower respiratory reactance as well as higher area of-reactance and lung clearance index values compared with controls (P<0.05).

Conclusion: Our study indicates that children with asthma have a reduced lung function in concert with impaired immune responses and altered immune cell subsets. Improving our understanding of immune responses to viral and bacterial infection in childhood asthma can help to tailor management of the disease.

Keywords: asthma; children; innate immune response; innate lymphoid cells; lung function.

Figure 1

Effects of RV1B stimulation on cytokine responses of PBMCs. PBMCs from children with asthma (n=48) and healthy controls (n=14) were exposed to media or RV1B (MOI=20) for 48h. Bars represent median (interquartile range). Data adjusted for the levels in uninfected PBMCs (control). Plot represents median with interquartile ranges and individual’s values are represented by dots. PBMC, peripheral blood mononuclear cells; RV, rhinovirus; IFN, interferon.

Figure 2

Effects of HDM stimulation on cytokine responses of PBMCs. PBMCs from children with asthma (n=48) and healthy controls (n=14) were exposed to media or HDM for 48h. Bars represent median (interquartile range). Data adjusted for the levels in uninfected PBMCs (control). Plot represents median with interquartile ranges and individual’s values are represented by dots. PBMC, peripheral blood mononuclear cells; HDM, house dust mite; IL, interleukin.

Figure 3

Effects of LPS stimulation on cytokine responses of PBMCs. PBMCs from children with asthma (n=48) and healthy controls (n=14) were exposed to media or LPS for 48h. Bars represent median (interquartile range). Data adjusted for the levels in uninfected PBMCs (control). Plot represents median with interquartile ranges and individual’s values are represented by dots. PBMC, peripheral blood mononuclear cells; LPS, lipopolysaccharide; IFN, interferon.

Figure 4

Frequency of (A) ILC1, (B) ILC2 and (C) NCR- ILC3 in children with asthma and healthy controls. Bars represent median (interquartile range). Immune cell phenotyping was performed in whole blood using a lyse-wash procedure. Cells are per 10⁶ CD45⁺ cells. Plot represents median with interquartile ranges and individual’s values are represented by dots. ILCs, innate lymphoid cells; NCR, natural cytotoxicity receptor.