Respiratory Syncytical Virus–induced Chemokine Expression in the Lower Airways

Abstract

Characterization of chemokine expression patterns in virus-infected epithelial cells provides important clues to the pathophysiology of such infections. The aim of this study was to determine the chemokine response pattern of respiratory epithelium when infected with respiratory syncytial virus (RSV). Macrophage inflammatory protein-1-alpha (MIP-1-alpha), interleukin-8 (IL-8), and RANTES concentrations were measured from RSV-infected HEp-2, MRC-5, and WI-38 cell culture supernatants daily following infection. Additionally, MIP-1-alpha, IL-8, and RANTES concentrations were measured from lower respiratory secretions obtained from 10 intubated infants (0-24 mo) with RSV bronchiolitis, and from 10 control subjects. Our results indicate that respiratory epithelial cells respond to RSV infection by producing MIP-1-alpha, IL-8, and RANTES. Production of MIP-1-alpha required ongoing viral replication, whereas RANTES and IL-8 could be elicited by inactivated forms of the virus. MIP-1-alpha, RANTES, and IL-8 were also present in lower airway secretions obtained from patients with RSV bronchiolitis. Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), the eosinophil secretory ribonucleases, were detected in lower airway secretions from RSV-infected patients; ECP concentrations correlated with MIP-1-alpha concentrations (r = 0.93). We conclude that MIP-1-alpha is present in the lower airways during severe RSV disease. The correlation between MIP-1-alpha and ECP concentrations suggests a role for eosinophil degranulation products in the pathogenesis of RSV bronchiolitis.

Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus

“…Eosinophil recruitment and degranulation in lung tissue has been observed in response to RSV infection in humans; [2][3][4]35,36 however, the contributions of this cell to disease and innate immunity have not been clearly defined. We demonstrate here that an airway eosinophilia present constitutively in hypereosinophilic (IL-5 Tg) mice or introduced by transfer of eosinophils directly to the lungs, results in the accelerated clearance of RSV virions and reduction in associated airway dysfunction, including mucus hypersecretion and AHR.…”

Bovine respiratory syncytial virus infection

“…[15,52,53,58,95,99], which contribute to inflammation by recruiting neutrophils, macrophages and lymphocytes to the airways. Although less well studied, BRSV infection induces a similar up-regulation of pro-inflammatory chemokines and cytokines in the bovine lung.…”

“…Nevertheless, the virokinin did not have any direct chemoattractant proprieties on inflammatory cells, in vitro [153]. The chemokines RANTES (CCL5) and MIP-1α (CCL3) are potent attractants for human eosinophils and there is a correlation between levels of MIP-1α and eosinophil cationic protein in the lower airways of infants with severe HRSV disease [58]. However, there were no significant differences in mRNA for either RANTES or MIP-1α in the lungs of calves infected with the F mutant viruses, suggesting that these chemokines may not be involved in eosinophil recruitment in the calf [153].…”

CXCR2 Regulates Respiratory Syncytial Virus-Induced Airway Hyperreactivity and Mucus Overproduction

“…Therefore, one can imagine that the chemokine profile that follows a particular stimulus will dictate the subsequent inflammatory response. In vitro, RSV infection of human airway epithelial cells has shown that a number of chemokines can be induced, including RANTES, macrophage-inflammatory protein (MIP) 1␣, MIP-1␤, monocyte-derived chemokine; I-309; Exodus; Fractlkine; IL-8; Gro-␣, -␤, and -␥; epithelial neutrophilactivating protein 78; and IFN-inducible T cell ␣ chemoattractant (11)(12)(13)(14). In vivo analyses of sputum samples from infants with RSV show elevated levels of IL-8 (15,16), a CXC chemokine capable of binding CXCR1 and CXCR2 (17).…”