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

作者：Han Mingyuan; Chung Yutein; Hong Jun Young; Rajput Charu; Lei Jing; Hinde Joanna L; Chen Qiang; Weng Steven P; Bentley J Kelley; Hershenson Marc B^*

来源：Journal of Allergy and Clinical Immunology, 2016, 138(6): 1619-1630.

DOI：10.1016/j.jaci.2016.01.037

• Alternative activation
• asthma
• CD11b
• exacerbation
• M2 macrophage

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 1 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.

• 出版日期2016-12