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Background Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. Methods We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA-sequencing. Rhinovirus-derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B-cell differentiation in response rhinovirus stimulation. Protein expression of pro-inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. Results B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN-alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co-stimulation with rhinovirus and IFN-alpha upregulated pro-inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. Conclusion These findings add to the understanding of systemic effects of rhinovirus infections on B-cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses., Allergy, 77 (1), ISSN:0105-4538, ISSN:1398-9995

Publisher Summary This chapter reviews the epidemiological evidence implicating infectious pathogens as triggers and will discuss the mechanisms of interaction between the host–pathogen response and preexisting airway pathology that result in an exacerbation. Asthma is a multifaceted syndrome involving atopy, bronchial hyperreactivity, and IgE and non-IgE-mediated acute and chronic immune responses. The asthmatic airway is characterized by an infiltrate of eosinophils and of T-lymphocytes expressing the type 2 cytokines IL-4, IL-5, and IL-13. Trigger factors associated with acute exacerbations of asthma include exposure to environmental allergens, especially animals, molds, pollens and mites, cold, exercise, and drugs. The frequency of exacerbations is a major factor in the quality of life of patients with COPD. The typical clinical features of an exacerbation include increased dyspnea, wheezing, cough, sputum production, and worsened gas exchange. Although noninfectious causes of exacerbations such as allergy, air pollution, or inhaled irritants including cigarette smoke may be important, acute airway infections are the major precipitants. The infection and consequent host inflammatory response result in increased airway obstruction. The success of vaccination to prevent respiratory virus infections has been limited by significant variation within the major virus types causing disease. Currently much of the treatment of infective exacerbations of asthma and COPD is symptomatic, consisting of increased bronchodilators, either short-acting β 2—agonists in inhaled or intravenous form or anticholinergics or theophyllines, or supportive in the form of oxygen and in severe cases noninvasive or invasive ventilatory measures.

Publisher Summary Infection, in particular by respiratory viruses, plays an important role in triggering exacerbations and has also been implicated in the etiology of asthma and chronic obstructive pulmonary disease (COPD). This chapter reviews the epidemiological evidence that implicates infectious pathogens as triggers. The chapter also discusses the mechanisms of interaction between the host-pathogen response and preexisting airway pathology resulting in an exacerbation. Much of the treatment of infective exacerbations for both asthma and COPD is symptomatic, consisting of bronchodilators or supportive in the form of oxygen, and in severe cases it includes noninvasive or invasive ventilatory measures. The current therapy for virus-induced exacerbations of asthma and COPD relies on increased treatment of preexisting disease. Antibiotics are indicated for bacterial infections. The effective use of antiviral agents, particularly for influenza viruses, requires viral diagnosis, commencement of treatment early in the course of an exacerbation, or the targeting of high-risk groups for prophylaxis. Alternative strategies for drug development involve the identification of key factors common to exacerbations induced by a range of different viruses. Increased knowledge of the host–virus interaction can help in designing treatments that can increase virus clearance and minimize immunopathology.