Reviews and feature article
Host immune responses to rhinovirus: Mechanisms in asthma

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Viral respiratory infections can have a profound effect on many aspects of asthma including its inception, exacerbations, and, possibly, severity. Of the many viral respiratory infections that influence asthma, the common cold virus, rhinovirus, has emerged as the most frequent illness associated with exacerbations and other aspects of asthma. The mechanisms by which rhinovirus influences asthma are not fully established, but current evidence indicates that the immune response to this virus is critical in this process. Many airway cell types are involved in the immune response to rhinovirus, but most important are respiratory epithelial cells and possibly macrophages. Infection of epithelial cells generates a variety of proinflammatory mediators to attract inflammatory cells to the airway with a subsequent worsening of underlying disease. Furthermore, there is evidence that the epithelial airway antiviral response to rhinovirus may be defective in asthma. Therefore, understanding the immune response to rhinovirus is a key step in defining mechanisms of asthma, exacerbations, and, perhaps most importantly, improved treatment.

Section snippets

Rhinovirus

Rhinovirus is a genus of positive, single-stranded RNA viruses of the family Picornaviridae. Thus far, there are >100 rhinovirus serotypes identified, with serotype defined on the ability of a given serum to neutralize growth of a given strain of virus in cell culture.7 The rhinovirus capsid, which protects the central RNA core, is composed of 60 copies of each of 4 structural proteins. Virus protein 1 (VP1), VP2, and VP3 are located on the capsid surface and are responsible for its antigenic

Epithelium

Rhinovirus, like most respiratory viruses, replicates primarily in airway ECs. In addition to attaching ICAM-1 to gain entry to the cell, rhinovirus infection induces expression of ICAM-1 to further the availability of receptors for rhinovirus to bind to and infect the cell.24 Experimental infection of bronchial ECs with rhinovirus results in little cellular damage, a pattern of response that suggests that rhinovirus-induced asthma exacerbations occur through mechanisms other than direct

Macrophages

Macrophages are the most numerous cell type found in the airway lumen. Rhinovirus can attach to airway macrophages but may have limited replication in this cell.29, 30 More importantly, the interaction between rhinovirus and macrophages stimulates secretion of proinflammatory cytokines such as IL-1, IL-8, TNF-α, IFN-γ, and macrophage inflammatory protein (MIP)–1α.29, 30, 31, 32, 33 TNF-α induction of EC expression of ICAM-1 allows for leukocyte trafficking to areas of infection but also

T cells

Bronchial biopsies of subjects with asthma and control subjects with an experimental rhinovirus infection show T-cell infiltration of the airway epithelium and submucosa.41 Peripheral blood lymphopenia also occurs during a rhinovirus infection, possibly reflecting vigorous T-cell recruitment to the lung.58 Both airway lymphocyte infiltration and peripheral blood lymphopenia correlate inversely with changes in bronchial hyperresponsiveness during rhinovirus infection and revert to baseline

What are the products generated?

Products generated in response to rhinovirus infection by structural and immune cells have both effector and regulatory functions. The chemotactic cytokines, IL-8, RANTES, and MIP-1α, are increased with rhinovirus infection and correlate with the severity of cold symptoms.18, 26, 67, 68, 69 IL-8 is produced by ECs and macrophages and serves primarily as a chemoattractant for neutrophils. RANTES attracts eosinophils and can induce eosinophil degranulation.69 MIP-1α is a chemokine for lymphocytes

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    (Supported by an educational grant from Merck & Co., Inc.)

    Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

    Supported by National Institutes of Health–National Heart, Lung, and Blood Institute grant no. HL069116 and National Institutes of Health–National Institute of Allergy and Infectious Diseases grant no. T32 AI007635.

    Terms in boldface and italics are defined in the glossary on page 672.

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