title: Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and -independent manner.
abstract: BACKGROUND
  CpG administration abolishes airway inflammation and remodeling in acute models of allergic airway disease.
  
  
  METHODS
  Herein, we investigated the therapeutic effect of CpG in a chronic fungal model of asthma. TLR9+/+ and TLR9-/- mice were sensitized to soluble Aspergillus fumigatus antigens and challenged with live A. fumigatus conidia. Mice were treated with intraperitoneal (IP) or intranasal (IN) CpG, or left untreated 14-28 days after conidium challenge. All features of allergic airway disease were attenuated in TLR9+/+ mice treated with IN CpG, including airway hyperresponsiveness (AHR), mucus production, and peribronchial fibrosis.
  
  
  RESULTS
  TLR9-/- mice treated with IN CpG exhibited attenuated airway remodeling but not AHR. Whole-lung IL-12 levels were significantly elevated in both TLR9+/+ and TLR9-/- mice receiving IN CpG but not in either group receiving IP CpG. Whole-lung IL-10 levels were significantly elevated in IN CpG-treated TLR9+/+ mice but not in TLR9-/- mice receiving IN CpG. Increased whole-lung transcript and protein levels of the scavenger receptors SR-A and MARCO were observed in TLR9-/- mice compared with TLR9+/+ mice, possibly accounting for the CpG responsiveness in the knockout group.
  
  
  CONCLUSIONS
  Together, these data show that IN CpG has a therapeutic effect during established fungal asthma, which is TLR9 dependent and independent.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
authors.forename: Hemanth
authors.initials: H
authors.lastname: Ramaprakash
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000281:Administration, Intranasal; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity; D001249:Asthma / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000628:therapy; D054357:Chemokine CXCL10 / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016898:Interferon-alpha / Q000235:genetics; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000473:pathology / Q000628:therapy; D011971:Receptors, Immunologic / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D016898:Interferon-alpha; C092228:Marco protein, mouse; D009838:Oligodeoxyribonucleotides; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; C519703:TLR3 protein, mouse; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D018664:Interleukin-12; D007073:Immunoglobulin E