IL-33/ST2 immune responses to respiratory bacteria in pediatric asthma

Isabell Hentschke,Bettina Kroß,Patricia Haag,Christian Bogdan,Alexander Kiefer,Theodor Zimmermann,Susetta Finotto,Nikolaos G Papadopoulos,Paraskevi Xepapadaki,Anna Graser,Volker O Melichar

doi:10.1038/srep43426

Abstract

Here we investigated the relationship between local bacterial colonization and anti-bacterial immune responses in pre-school asthmatic and control children within the EU-wide study PreDicta. In this cohort of pre-school asthmatic children, nasopharyngeal colonization with Gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis was found to be associated with the highest interferon beta (IFNβ) and IL-33 levels in the nasal pharyngeal fluids (NPF). IL33R-ST2 was found induced in the blood of asthmatic children with additional Gram + bacteria in the nasopharynx (Gr+/−). Furthermore, asthmatic children had more episodes of infection that required antibiotic therapy than the control group. Treatment with antibiotics associated with reduced ST2 in blood cells of both asthmatic and control children and reduced IL-33 levels in the airways of asthmatic children. In the absence of Staphylococcus (S.) aureus in NPF, antibiotic therapy associated with decreased IL-33 levels in the NPF and lower ST2 values in the blood of control children but not of asthmatic children. These data suggest that, in asthmatic children, Gram- bacteria, which persist after antibiotic therapy, contributes to IL-33 locally and associated with Gr + bacteria colonization in the airways, inhibited IFN-β and in the absence of Staphylococcus (S.) aureus, induced ST2 bearing cells in their blood.

Highlights

Bacterial infections are known to trigger asthma exacerbations[1,2,3]
In this study we analyzed two cohorts of pre-school children one with and the second without asthma recruited within the Europe-wide study PreDicta (Post-infectious immune reprogramming and its association with persistence and chronicity of respiratory allergic diseases) and addressed the question whether the presence of distinct bacteria in their nasal pharyngeal fluids (NPF) as well as previous antibiotic therapy were associated with different antibacterial immune responses such as IL-33 and IFNβ production in their NPF and IL-33 receptor (IL-33R)/ST2 in the blood
In order to start analysing the influence of different bacterial colonization on asthma, we subdivided both cohorts in accordance to their bacterial nasopharyngeal colonization: Children that had saprophytic germs and bacteria that are physiological in the nasopharyngeal microbiome (PNC), or children that had additional or exclusively Gram negative bacteria in their nasopharyngeal fluid (Gram−)

Summary

Introduction

Bacterial infections are known to trigger asthma exacerbations[1,2,3]. It is known that recurrent viral and bacterial infections during childhood can promote the susceptibility to allergy and asthma[4]. IL-33 is a cytokine known to be released by damaged epithelial cells where infectious agents and/or allergens can spread through blood and into tissues. It is a cytokine of the innate immune response and activates innate lymphoid cells type 2 (ILC2) and Th2 cells to produce IL-5 and IL-13 after binding to its receptor suppression of tumorigenicity (ST2), termed IL-33 receptor (IL-33R). These Th2 cytokines were found to be increased in the nasopharynx of asthmatic patients[12]. In this study we analyzed two cohorts of pre-school children one with and the second without asthma recruited within the Europe-wide study PreDicta (Post-infectious immune reprogramming and its association with persistence and chronicity of respiratory allergic diseases) and addressed the question whether the presence of distinct bacteria in their nasal pharyngeal fluids (NPF) as well as previous antibiotic therapy were associated with different antibacterial immune responses such as IL-33 and IFNβ production in their NPF and IL-33R/ST2 in the blood

Methods

Results

Conclusion