Rhinovirus-Induced Airway Disease: A Model to Understand the Antiviral and Th2 Epithelial Immune Dysregulation in Childhood Asthma

Abstract

Rhinovirus (RV) infections account for most asthma exacerbations among children and adults, yet the fundamental mechanism responsible for why asthmatics are more susceptible to RV than otherwise healthy individuals remains largely unknown. Nonetheless, the use of models to understand the mechanisms of RV-induced airway disease in asthma has dramatically expanded our knowledge about the cellular and molecular pathogenesis of the disease. For instance, ground-breaking studies have recently established that the susceptibility to RV in asthmatic subjects is associated with a dysfunctional airway epithelial inflammatory response generated after innate recognition of viral-related molecules, such as double stranded (ds) RNA. This review summarizes the novel cardinal features of the asthmatic condition identified in the past few years through translational and experimental RV-based approaches. Specifically, we discuss the evidence demonstrating the presence of an abnormal innate antiviral immunity (airway epithelial secretion of type I and III interferons), exaggerated production of the master Th2 molecule thymic stromal lymphopoietin (TSLP), and altered antimicrobial host defense in the airways of asthmatic individuals with acute RV infection.

Conditional Reprogramming for Patient-Derived Cancer Models and Next-Generation Living Biobanks

“…Airway epithelial cells play an essential role in maintaining airway immune responses, while these epithelial cells in newborns/infants are difficult to obtain [134,135]. Brewington et al established CR nasal epithelial cells and measured activity of CFTR for pulmonary edema study [136].…”

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“…Em crianças que apresentaram respostas de citocinas de RV com menor indução de interferom e com altas citocinas pró-inflamatória constatou maior vulnerabilidade de exacerbação de asma grave durante a infância. Perez et al, (2015), afirma que grandes estudos de coorte de nascimentos identificaram que a infecção por RV nos primeiros 3 anos de vida está associada a um aumento de quase 10 vezes no risco de asma aos 6 anos, podendo ser maior a probabilidade em indivíduos com pré-disposição genética. RV é um patógeno viral agressivo que desencadeia respostas imunológicas anormais independente da sua replicação ativa, estudos das vias respiratórias humanas identificaram que a condição asmática é caracterizada por uma resposta de sinalização epitelial imune disfuncional após o reconhecimento inato de moléculas relacionadas ao vírus, como dsRNA.…”

Novel therapeutic approaches to simultaneously target rhinovirus infection and asthma/COPD pathogenesis

“…Little is known about the fundamental mechanisms responsible for the fact that asthmatics are more susceptible to RV-induced airway disease. Recent evidence points to an abnormal innate antiviral immunity (IFN dysregulation in airways), exaggerated production of inflammatory molecules such as the thymic stromal lymphopoietin, which primes Th2 responses, and an altered antibacterial host defense during acute RV infection 21 .…”