Innate Immune Responses by Respiratory Viruses, Including Rhinovirus, During Asthma Exacerbation

Abstract

Viral infection, especially with rhinovirus (RV), is a major cause of asthma exacerbation. The production of anti-viral cytokines such as interferon (IFN)-β and IFN-α from epithelial cells or dendritic cells is lower in patients with asthma or those with high IgE, which can contribute to viral-induced exacerbated disease in these patients. As for virus-related factors, RV species C (RV-C) induces more exacerbated disease than other RVs, including RV-B. Neutrophils activated by viral infection can induce eosinophilic airway inflammation through different mechanisms. Furthermore, virus-induced or virus-related proteins can directly activate eosinophils. For example, CXCL10, which is upregulated during viral infection, activates eosinophils in vitro. The role of innate immune responses, especially type-2 innate lymphoid cells (ILC2) and epithelial cell-related cytokines including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), in the development of viral-induced airway inflammation has recently been established. For example, RV infection induces the expression of IL-33 or IL-25, or increases the ratio of ILC2 in the asthmatic airway, which is correlated with the severity of exacerbation. A mouse model has further demonstrated that virus-induced mucous metaplasia and ILC2 expansion are suppressed by antagonizing or deleting IL-33, IL-25, or TSLP. For treatment, IFNs including IFN-β suppress not only viral replication but also ILC2 activation in vitro. Agonists of toll-like receptor (TLR) 3 or 7 can induce IFNs, which can then suppress viral replication and ILC2 activation. Therefore, if delivered in the airway, IFNs or TLR agonists could become innovative treatments for virus-induced asthma exacerbation.

Global prevalence of infections in newborns with respiratory complications: systematic review and meta-analysis

“…( 71 ). In this regard, it seems that human rhinovirus can induce or exacerbate asthma in infected hosts by changing the expression and/or production of inflammatory and pro-inflammatory mediators, which is a point worth considering ( 72 ).…”

The upregulation of peripheral CD3-CD56+CD16+ natural killer cells correlates with Th1/Th2 imbalance in asthma patients during acute upper respiratory viral infections

“…Respiratory viral infections, including RSV, in uenza virus, in uenza virus, and parain uenza virus infections, are greatly associated with asthma exacerbation that subsequently leads to wheezing and reduced expiratory ow rate 13,14 . Similarly, our study indicated a high incidence of RSV infection among asthma patients with acute upper respiratory viral infection.…”

“Liquid biopsy” - extracellular vesicles as potential novel players towards precision medicine in asthma

“…Viral respiratory infections, particularly with the rhinovirus (RV) and the respiratory syncytial virus (RSV), are major causes of asthma development and exacerbations ( 79 , 80 ). EVs offer new insight into the viral-induced chronic sequelae in the lung microenvironment.…”