Rhinovirus infection of allergen-sensitized and -challenged mice induces eotaxin release from functionally polarized macrophages.

Abstract

Human rhinovirus is responsible for the majority of virus-induced asthma exacerbations. To determine the immunologic mechanisms underlying rhinovirus (RV)-induced asthma exacerbations, we combined mouse models of allergic airways disease and human rhinovirus infection. We inoculated OVA-sensitized and challenged BALB/c mice with rhinovirus serotype 1B, a minor group strain capable of infecting mouse cells. Compared with sham-infected, OVA-treated mice, virus-infected mice showed increased lung infiltration with neutrophils, eosinophils and macrophages, airway cholinergic hyperresponsiveness, and increased lung expression of cytokines including eotaxin-1/CCL11, IL-4, IL-13, and IFN-gamma. Administration of anti-eotaxin-1 attenuated rhinovirus-induced airway eosinophilia and responsiveness. Immunohistochemical analysis showed eotaxin-1 in the lung macrophages of virus-infected, OVA-treated mice, and confocal fluorescence microscopy revealed colocalization of rhinovirus, eotaxin-1, and IL-4 in CD68-positive cells. RV inoculation of lung macrophages from OVA-treated, but not PBS-treated, mice induced expression of eotaxin-1, IL-4, and IL-13 ex vivo. Macrophages from OVA-treated mice showed increased expression of arginase-1, Ym-1, Mgl-2, and IL-10, indicating a shift in macrophage activation status. Depletion of macrophages from OVA-sensitized and -challenged mice reduced eosinophilic inflammation and airways responsiveness following RV infection. We conclude that augmented airway eosinophilic inflammation and hyperresponsiveness in RV-infected mice with allergic airways disease is directed in part by eotaxin-1. Airway macrophages from mice with allergic airways disease demonstrate a change in activation state characterized in part by altered eotaxin and IL-4 production in response to RV infection. These data provide a new paradigm to explain RV-induced asthma exacerbations.

• Authors: Deepti R Nagarkar, Emily R Bowman, Dina Schneider, Qiong Wang, Jee Shim, Ying Zhao, Marisa J Linn, Christina L McHenry, Babina Gosangi, J Kelley Bentley, Wan C Tsai, Umadevi S Sajjan, Nicholas W Lukacs, Marc B Hershenson
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 4 Pg. 2525-35 (Aug 15 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20644177 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 protein, mouse
• Chemokine CCL11
• Cytokines
• Inflammation Mediators
• Ovalbumin

Topics

• Animals
• Antigens, CD (immunology, metabolism)
• Antigens, Differentiation, Myelomonocytic (immunology, metabolism)
• Bronchial Hyperreactivity (immunology, metabolism)
• Chemokine CCL11 (genetics, immunology, metabolism)
• Cytokines (genetics, immunology, metabolism)
• Eosinophils (immunology, metabolism, pathology)
• HeLa Cells
• Humans
• Immunohistochemistry
• Inflammation (immunology, metabolism)
• Inflammation Mediators (immunology, metabolism)
• Lung (immunology, metabolism, pathology)
• Macrophages, Alveolar (immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Microscopy, Confocal
• Ovalbumin (immunology)
• Picornaviridae Infections (immunology, virology)
• Reverse Transcriptase Polymerase Chain Reaction
• Rhinovirus (immunology)