Rhinovirus infection induces interleukin-13 production from CD11b-positive, M2-polarized exudative macrophages.

Abstract

Rhinovirus (RV) causes asthma exacerbations. Previously, we showed that adherent bronchoalveolar cells from allergen-treated mice produce IL-13 when stimulated with RV ex vivo, implicating cells of the monocyte/macrophage lineage in viral-induced airway inflammation. In this study, we hypothesized that RV infection of allergen-treated mice results in IL-13 production by CD11b+ exudative macrophages in vivo. We sensitized and challenged BALB/c mice with ovalbumin (OVA), after which mice were inoculated with RV or sham HeLa cell lysate. After 1 day, lungs were harvested, and cell suspensions were analyzed by flow cytometry. We repeated this process in IL-13 reporter mice, CD11b-DTR mice in which diphtheria toxin selectively depletes CD11b+ cells, and chemokine receptor 2 (CCR2) null mice. We found that lungs of mice infected with RV alone showed increases in CD45+, CD68+, F4/80+, Ly6C+, and CD11b(high) cells, indicating an influx of inflammatory monocytes and exudative macrophages. The combination of OVA and RV had synergistic effects on the exudative macrophage number. However, CD11b+ cells from OVA-treated, RV-infected mice showed M2 polarization, including expression of CD206 and CD301 and production of IL-13. Similar results were obtained in IL-13 reporter mice. Diphtheria toxin depleted CD11b+, IL-13-producing cells in OVA-treated, RV-infected, CD11b-DTR mice, decreasing airway inflammation and responsiveness. CD11b+, Ly6C+ cells were reduced in CCR2 knockout mice. We conclude that, in contrast to naive mice, RV infection of mice with allergic airways disease induces an influx of IL-13-producing CD11b+ exudative macrophages bearing M2 macrophage markers. This finding further implicates alternatively activated macrophages in RV-induced asthma exacerbations.

• Authors: Yutein Chung, Jun Young Hong, Jing Lei, Qiang Chen, J Kelley Bentley, Marc B Hershenson
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 52 Issue 2 Pg. 205-16 (Feb 2015) ISSN: 1535-4989 [Electronic] United States
• PMID: 25029349 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Allergens
• CD11b Antigen
• Interleukin-13
• Ovalbumin

Topics

• Allergens (immunology)
• Animals
• Asthma (immunology, metabolism, virology)
• CD11b Antigen (immunology)
• Cell Polarity
• Disease Models, Animal
• Female
• Inflammation (immunology)
• Interleukin-13 (biosynthesis)
• Lung (immunology, metabolism, virology)
• Macrophages (immunology, metabolism)
• Mice, Inbred C57BL
• Ovalbumin (immunology)
• Rhinovirus