title: Toll-like receptor 2-expressing macrophages are required and sufficient for rhinovirus-induced airway inflammation.
abstract: 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.
  
  
  
  We hypothesize that TLR2+macrophages are required and sufficient for rhinovirus-induced airway inflammation in vivo.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Yutein
authors.initials: Y
authors.lastname: Chung
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Jun
authors.initials: J
authors.lastname: Young Hong
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Charu
authors.initials: C
authors.lastname: Rajput
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Jing
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Hinde
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Weng
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich.
authors.forename: J Kelley
authors.initials: JK
authors.lastname: Bentley
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Mich; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Mich. Electronic address: mhershen@umich.edu.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010850:Picornaviridae Infections / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
keywords: Alternative activation; CD11b; M2 macrophage; asthma; exacerbation