title: Attenuation of experimental asthma by mycobacterial protein combined with CpG requires a TLR9-dependent IFN-γ-CCR2 signalling circuit.
abstract: BACKGROUND
  Allergic asthma is a chronic pulmonary disease characterized by a Th2 inflammatory response. The modulation of a Th2 immune response based on immune deviation to a Th1 pattern or induction and migration of regulatory T cells to the lungs constitutes one of the major therapeutic approaches that is being investigated for the treatment of allergic asthma. The potentials of Mycobacterium leprae 65-kD heat-shock protein or Toll-like receptor 9 ligand (CpG oligodeoxynucleotides) as immune modulators for the treatment of airway allergic disease have been studied individually.
  
  
  OBJECTIVE
  Mycobacterial protein combined with CpG was used as immunotherapy for airway allergy.
  
  
  METHODS
  Using an ovalbumin-induced asthma model, mice were sensitized and challenged, and then treated with mycobacterial heat-shock protein (Hsp65) combined with CpG.
  
  
  RESULTS
  The treatment of mice with established allergy led to the attenuation of eosinophilia, Th2 cytokines and airway hyperresponsiveness. Hsp65 plus CpG treatment also induced an increase in OVA-specific IFN-γ levels and in the frequency of lung inflammatory monocytes. Moreover, we show that the reduction of eosinophilia and the recruitment of inflammatory monocytes to the lungs required early triggering of TLR9, IFN-γ and CCR2 by immunotherapy components.
  
  
  CONCLUSIONS
  In addition to immune deviation to a Th1 response in the modulation of Th2 allergic inflammation, our findings also attribute an important role to the innate response mediated by TLR9, associated with the recruitment of CCR2-dependent monocytes.
  
  
  CONCLUSIONS
  Our findings show that the Hsp65/CpG treatment is a promising strategy for consideration in translational studies.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: R Q
authors.initials: RQ
authors.lastname: Prado
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: T B
authors.initials: TB
authors.lastname: Bertolini
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: A R
authors.initials: AR
authors.lastname: Piñeros
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: A F
authors.initials: AF
authors.lastname: Gembre
authors.affiliation: Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: S G
authors.initials: SG
authors.lastname: Ramos
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: C L
authors.initials: CL
authors.lastname: Silva
authors.affiliation: Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Borges
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: V L D
authors.initials: VL
authors.lastname: Bonato
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000494:pharmacology*; D018834:Chaperonin 60 / Q000494:pharmacology*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009166:Mycobacterium leprae; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; C515335:Ccr2 protein, mouse; D018834:Chaperonin 60; D009838:Oligodeoxyribonucleotides; D054390:Receptors, CCR2; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C074119:heat-shock protein 65, Mycobacterium; D007371:Interferon-gamma
keywords: CpG; TLR9; experimental asthma; mycobacterial protein