Abstract
Interleukin- 33 (IL-33) is an epithelial-derived cytokine that initiates type 2 immune responses to allergens, though whether IL-33 has the ability to modify responses to respiratory viral infections remains unclear. This study aimed to investigate the effects of IL-33 on rhinovirus (RV)-induced immune responses by circulating leukocytes from people with allergic asthma, and how this response may differ from non-allergic controls. Our experimental approach involved co-exposing peripheral blood mononuclear cells to IL-33 and RV in order to model how the functions of virus-responsive lymphocytes could be modified after recruitment to an airway environment enriched in IL-33. In the current study, IL-33 enhanced RV-induced IL-5 and IL-13 release by cells from people with allergic asthma, but had no effect on IL-5 and IL-13 production by cells from healthy donors. In asthmatic individuals, IL-33 also enhanced mRNA and surface protein expression of ST2 (the IL-33 receptor IL1RL1), while soluble ST2 concentrations were low. In contrast, IL-33 had no effect on mRNA and surface expression of ST2 in healthy individuals. In people with allergic asthma, RV-activated ST2+ innate lymphoid cells (ST2+ILC) were the predominant source of IL-33 augmented IL-13 release. In contrast, RV-activated natural killer cells (NK cells) were the predominant source of IL-33 augmented IFNγ release in healthy individuals. This suggests that the effects of IL-33 on the cellular immune response to RV differ between asthmatic and healthy individuals. These findings provide a mechanism by which RV infections and IL-33 might interact in asthmatic individuals to exacerbate type 2 immune responses and allergic airway inflammation.
Highlights
Acute exacerbations make a major contribution to the burden of asthma, with respiratory viral infections, in particular, rhinoviruses (RV), triggering most exacerbations
This study demonstrates that Interleukin- 33 (IL-33) has distinct effects on the in vitro cellular response to RV in asthmatic and healthy individuals
Immune response, but has no effect on type 2 responses. This is associated with differential regulation of the IL-33 receptor, with higher stimulated ST2 expression in cells from asthmatic than in cells from healthy individuals
Summary
Acute exacerbations make a major contribution to the burden of asthma, with respiratory viral infections, in particular, rhinoviruses (RV), triggering most exacerbations. Even though RV is usually confined to epithelial cells lining the upper respiratory tract and may IL-33 and RV-Induced Type 2 Immunity in Asthma sometimes involve the lower respiratory tract, there is strong evidence that systemic immune function plays an important role in host defense against RV infections. High titers of specific neutralizing antibodies are protective against experimental RV infections [1]. The capacity of circulating T-cells to proliferate and produce IFNγ and IL-10 after RV stimulation in vitro is inversely associated with viral load during an RV infection [2]. A large birth cohort study has shown that RV-activated blood mononuclear cells exhibit varying cytokine response patterns in vitro that are associated with different clinical outcomes [3]
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