Host immune responses to rhinovirus: mechanisms in asthma

Abstract

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.

FIG 1

EC response to rhinovirus infection. ECs secrete cytokines that attract neutrophils, eosinophils, and lymphocytes. Macrophages may be infected in part by rhinovirus released from the epithelium.

FIG 2

Immune cell response to rhinovirus. Innate immune response from macrophages includes secretion of cytokines, which recruit additional innate and adaptive immune cell responses. ECP, Eosinophilic cationic protein; EDN, eosinophil-derived neurotoxin.

FIG 3

Consequences of immune response to rhinovirus and altered airway responses in asthma.

FIG 4

Antiviral response to rhinovirus in a healthy subject versus a subject with asthma.

FIG 5

Interface and interactions between antirhinovirus therapeutic agents and regulation of the immune response to rhinovirus. Experimental agents in boldface; proposed therapies in italics.