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.
(Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)