Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness - PubMed (original) (raw)

Review

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

Michael R Edwards et al. J Allergy Clin Immunol. 2017 Oct.

Abstract

Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with TH2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and TH2 mediators. With the renewed interest in anti-TH2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis.

Keywords: T(H)2; Virus; allergic inflammation; asthma; interferon.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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Figures

Fig 1

Fig 1

Overview of additive or synergistic effects of allergen exposure and viral infection driving both pro-TH2 and IgE/TH2 inflammation. Viral infection damages the epithelial barrier and results in the pro-TH2 cytokines IL-33, IL-25, and thymic stromal lymphopoietin. These cytokines act on ILC2s, DCs, and TH2 cells, resulting in production of the TH2 cytokines IL-13, IL-4, and IL-5. These cytokines have a central role in allergic asthma: IL-4 and IL-13 drive antibody class-switching to IgE in B cells, IL-13 can act also on airway smooth muscle cells, causing bronchoconstriction and contributing to airway remodeling, and IL-5 contributes to eosinophil production. Actions of IL-4 and IL-13 and viruses on airway epithelial cells can induce the eotaxins that attract eosinophils and the chemokines macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC), which attract TH2 cells into the airway. IgE cross-linking by allergen on mast cells produces histamine, leukotrienes, and the prostaglandins PGD2 and PGE2, which further promote bronchoconstriction. PGD2 binds chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) and activates basophils, TH2 cells, and ILC2s. Viruses can also cause oxidative stress, and pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) production can lead to the proinflammatory cytokines IL-1α/β, TNF, and IL-6. This generally results in neutrophilic inflammation and activation of macrophages. Allergen-induced IL-1α can also promote the pro-TH2 response and lead to further IL-33 production and activation of ILC2s. ENA-78, Epithelial-derived neutrophil-activating protein 78; GRO-α, melanoma growth stimulating activity-α; IL-4R, IL-4 receptor; IL-13R, IL-13 receptor; IL-25R, IL-25 receptor; IL-33R, IL-33 receptor.

Fig 2

Fig 2

Summary of mechanisms of reciprocal negative regulation of type I and III interferons and TH2 pathways in asthmatic patients. TH2 cytokines can negatively regulate virus-induced interferons; cross-linking of cell-bound IgE on DCs prevents virus-induced IFN-α on infection; pretreatment of HBECs with IL-4, IL-13, or TGF-β results in low IFN-β and IL-29 induction on infection; and IL-33 can act on DCs and reduce IRAK levels and hence IFN-α induction on infection. Interferons can suppress TH2 responses; pretreatment of T cells with IFN-α/β reduces GATA-3 and IL-5 levels in TH2 cells; viruses or TLR7 agonists produce IFN-α/β from DCs, which act on TH2 cells to reduce level of IL-4, IL-5, and IL-13; and IFN-β pretreatment of ILC2s causes a reduction in IL-4, IL-5, and IL-13. Finally, IL-28A (IFN-λ) acts on DCs to reduce OX40 ligand and prevent TH2 cell expression of IL-5 and IL-13. BECs, Bronchial epithelial cell; pDCs, plasmacytoid dendritic cells.

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