title: Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation.
abstract: BACKGROUND
  The human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject.
  
  
  OBJECTIVE
  Previous studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses in vitro and in vivo.
  
  
  METHODS
  The skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In in vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in in vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters.
  
  
  RESULTS
  In healthy subjects, but not in atopic ones, the relative abundance of Acinetobacter species was associated with the expression of anti-inflammatory molecules by PBMCs. Moreover, healthy subjects exhibited a robust balance between anti-inflammatory and TH1/TH2 gene expression, which was related to the composition of the skin microbiota. In cell assays and in a mouse model, Acinetobacter species induced strong TH1 and anti-inflammatory responses by immune cells and skin cells and protected against allergic sensitization and lung inflammation through the skin.
  
  
  CONCLUSIONS
  These results support the hypothesis that skin commensals play an important role in tuning the balance of TH1, TH2, and anti-inflammatory responses to environmental allergens.
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Nanna
authors.initials: N
authors.lastname: Fyhrquist
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Lasse
authors.initials: L
authors.lastname: Ruokolainen
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Alina
authors.initials: A
authors.lastname: Suomalainen
authors.affiliation: Molecular Immunology Group, Turku Centre for Biotechnology, Turku, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Lehtimäki
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Veckman
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Vendelin
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Piia
authors.initials: P
authors.lastname: Karisola
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Maili
authors.initials: M
authors.lastname: Lehto
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Terhi
authors.initials: T
authors.lastname: Savinko
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, and Helsinki University Central Hospital Laboratory (HUSLAB), Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Jarva
authors.affiliation: Haartman Institute, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, and Helsinki University Central Hospital Laboratory (HUSLAB), Helsinki, Finland.
authors.forename: Timo U
authors.initials: TU
authors.lastname: Kosunen
authors.affiliation: Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Auvinen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Lars
authors.initials: L
authors.lastname: Paulin
authors.affiliation: Allergy Department, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: von Hertzen
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Laatikainen
authors.affiliation: Allergy Department, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Mäkelä
authors.affiliation: Allergy Department, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Tari
authors.initials: T
authors.lastname: Haahtela
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Dario
authors.initials: D
authors.lastname: Greco
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Hanski
authors.affiliation: Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland. Electronic address: harri.alenius@ttl.fi.
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000150:Acinetobacter / Q000235:genetics; D000293:Adolescent; D000485:Allergens / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells; D020869:Gene Expression Profiling; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D015603:Keratinocytes; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D064307:Microbiota; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012867:Skin / Q000276:immunology / Q000382:microbiology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S; D010047:Ovalbumin
keywords: Acinetobacter species; Atopy; Gammaproteobacteria; PBMC; anti-inflammatory gene expression; dendritic cells; keratinocytes; mouse asthma model