Toll-like receptor 2-expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation.

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.