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.

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.

Keywords: Acinetobacter species; Atopy; Gammaproteobacteria; PBMC; anti-inflammatory gene expression; dendritic cells; keratinocytes; mouse asthma model.