TY - JOUR
T1 - Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation
AU - Fyhrquist, Nanna
AU - Ruokolainen, Lasse
AU - Suomalainen, Alina
AU - Lehtimäki, Sari
AU - Veckman, Ville
AU - Vendelin, Johanna
AU - Karisola, Piia
AU - Lehto, Maili
AU - Savinko, Terhi
AU - Jarva, Hanna
AU - Kosunen, Timo U
AU - Corander, Jukka
AU - Auvinen, Petri
AU - Paulin, Lars
AU - von Hertzen, Leena
AU - Laatikainen, Tiina
AU - Mäkelä, Mika
AU - Haahtela, Tari
AU - Greco, Dario
AU - Hanski, Ilkka
AU - Alenius, Harri
N1 - Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
PY - 2014/12
Y1 - 2014/12
N2 - 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.
AB - 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.
KW - Acinetobacter/genetics
KW - Adolescent
KW - Allergens/immunology
KW - Animals
KW - Bronchoalveolar Lavage Fluid/cytology
KW - Cells, Cultured
KW - Cytokines/genetics
KW - Dendritic Cells
KW - Gene Expression Profiling
KW - Humans
KW - Hypersensitivity/immunology
KW - Keratinocytes
KW - Leukocytes, Mononuclear/immunology
KW - Mice
KW - Microbiota
KW - Ovalbumin/immunology
KW - Pneumonia/immunology
KW - RNA, Bacterial/genetics
KW - RNA, Messenger/metabolism
KW - RNA, Ribosomal, 16S/genetics
KW - Skin/immunology
KW - Th1 Cells/immunology
KW - Th2 Cells/immunology
U2 - 10.1016/j.jaci.2014.07.059
DO - 10.1016/j.jaci.2014.07.059
M3 - Article
C2 - 25262465
SN - 0091-6749
VL - 134
SP - 1301-1309.e11
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -