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

Am J Respir Cell Mol Biol. 2015 Feb;52(2):205-16. doi: 10.1165/rcmb.2014-0068OC.


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.

Keywords: alternative activation; asthma; exacerbation; innate immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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


  • Allergens
  • CD11b Antigen
  • Interleukin-13
  • Ovalbumin