title: Inhibition of IFN-γ promotes anti-asthma effect of Mycobacterium bovis Bacillus Calmette-Guerin neonatal vaccination: a murine asthma model.
abstract: OBJECTIVE
  The Mycobacterium bovis Bacillus Calmette-Guerin (BCG) neonatal vaccination inhibits allergy-induced pathologic changes. However, the mechanisms underlying this process are unclear. This study aimed to investigate the role of interferon (IFN)-γ and interleukin (IL)-17 in the protective effects of the BCG neonatal vaccination on allergic pulmonary inflammation and airway hyperresponsiveness (AHR).
  
  
  METHODS
  Wild type (WT)-neonate and IL-17 knock out (KO) neonate mice were vaccinated with BCG. A murine asthma model was developed by sensitization and then challenging with ovalbumin (OVA). Recombinant IL-17 or recombinant IFN-γ was delivered to the airway to overexpress IL-17 or IFN-γ. An anti-IFN-γ neutralizing antibody was used to block the effects of IFN-γ.
  
  
  RESULTS
  We found exogenous IL-17 delivered to the airway reversed the anti-asthma effects of the neonatal BCG vaccination. BCG neonatal vaccination further reduced OVA-induced inflammation and AHR in IL-17 KO mice. Inhibition of IFN-γ in BCG neonatal vaccinated OVA-induced asthma model mice led to a further reduction in airway inflammation and AHR. In addition, airway inflammation and AHR were robust following treatment with exogenous IFN-γ. Neutralizing IL-17 was not sufficient to block OVA-induced airway inflammation and AHR. In IL-17 KO mice, airway inflammation and AHR did not occur following treatment with an anti-IFN-γ neutralizing antibody.
  
  
  CONCLUSIONS
  In an OVA-induced murine asthma model, inhibition of IFN-γ enhanced the anti-asthma effects of BCG neonatal vaccination.
authors.affiliation: Department of Respiratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Respiratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neonatology, The Affiliated Hospital of Zunyi Medical College, Zunyi 563003, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Li J
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pediatrics in Chongqing, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Xiao H
authors.initials: XH
authors.lastname: Xie
authors.affiliation: Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Respiratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Zheng X
authors.initials: ZX
authors.lastname: Luo
authors.affiliation: Department of Nephrology and Immunology Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Xiao D
authors.initials: XD
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, PR China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Respiratory Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400014, PR China. Electronic address: emliu186@hotmail.com.
authors.forename: En M
authors.initials: EM
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001249:Asthma / Q000517:prevention & control*; D001500:BCG Vaccine / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D007249:Inflammation / Q000517:prevention & control*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D011994:Recombinant Proteins
chemical_list: D057134:Antibodies, Neutralizing; D001500:BCG Vaccine; D020381:Interleukin-17; D011994:Recombinant Proteins; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: Asthma; IFN-γ; IL-17; Mycobacterium bovis Bacillus Calmette– Guerin