Background We have shown that rhinovirus, a cause of asthma exacerbation, colocalizes with CD68+ and CD11b+ airway macrophages after experimental infection in human subjects. We have also shown that rhinovirus-induced cytokine expression is abolished in Toll-like receptor (TLR2)−/− bone marrow–derived macrophages. Objective We hypothesize that TLR2+ macrophages are required and sufficient for rhinovirus-induced airway inflammation in vivo. Methods Naive and ovalbumin (OVA)–sensitized and challenged C57BL/6 wild-type and TLR2−/− mice were infected with RV1B, followed by IgG or anti-TLR2, to determine the requirement and sufficiency of TLR2 for rhinovirus-induced airway responses. Bone marrow chimera experiments using OVA-treated C57BL/6 and TLR2−/− mice were also performed. Finally, naive TLR2−/− mice underwent intranasal transfer of bone marrow–derived wild-type macrophages. Results RV1B infection of naive wild-type mice induced an influx of airway neutrophils and CD11b+ exudative macrophages, which was reduced in TLR2−/− mice. After allergen exposure, rhinovirus-induced neutrophilic and eosinophilic airway inflammation and hyperresponsiveness were reduced in TLR2−/− and anti-TLR2–treated mice. Transfer of TLR2−/− bone marrow into wild-type, OVA-treated C57BL/6 mice blocked rhinovirus-induced airway responses, whereas transfer of wild-type marrow to TLR2−/− mice restored them. Finally, transfer of wild-type macrophages to naive TLR2−/− mice was sufficient for neutrophilic inflammation after rhinovirus infection, whereas macrophages treated with IL-4 (to induce M2 polarization) were sufficient for eosinophilic inflammation, mucous metaplasia, and airways hyperresponsiveness. Conclusions TLR2 is required for early inflammatory responses induced by rhinovirus, and TLR2+ macrophages are sufficient to confer airway inflammation to TLR2−/− mice, with the pattern of inflammation depending on the macrophage activation state.
Bibliographical notePublisher Copyright:
© 2016 American Academy of Allergy, Asthma & Immunology
All Science Journal Classification (ASJC) codes
- Immunology and Allergy