Nanna Fyhrquist1, Lasse Ruokolainen2, Alina Suomalainen1, Sari Lehtimäki3, Ville Veckman1, Johanna Vendelin1, Piia Karisola1, Maili Lehto1, Terhi Savinko4, Hanna Jarva5, Timo U Kosunen5, Jukka Corander6, Petri Auvinen4, Lars Paulin4, Leena von Hertzen7, Tiina Laatikainen8, Mika Mäkelä7, Tari Haahtela7, Dario Greco1, Ilkka Hanski2, Harri Alenius9. 1. Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland. 2. Department of Biosciences, University of Helsinki, Helsinki, Finland. 3. Molecular Immunology Group, Turku Centre for Biotechnology, Turku, Finland. 4. Institute of Biotechnology, University of Helsinki, Helsinki, Finland. 5. Haartman Institute, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, and Helsinki University Central Hospital Laboratory (HUSLAB), Helsinki, Finland. 6. Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland. 7. Allergy Department, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland. 8. 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. 9. Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland. Electronic address: harri.alenius@ttl.fi.
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. CONCLUSION: 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.
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. CONCLUSION: 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.
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