Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation

J Allergy Clin Immunol. 2014 Dec;134(6):1301-1309.e11. doi: 10.1016/j.jaci.2014.07.059. Epub 2014 Sep 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter* / genetics
  • Adolescent
  • Allergens / immunology
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cells, Cultured
  • Cytokines / genetics
  • Dendritic Cells
  • Gene Expression Profiling
  • Humans
  • Hypersensitivity / immunology*
  • Keratinocytes
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Mice
  • Microbiota*
  • Ovalbumin / immunology
  • Pneumonia / immunology*
  • RNA, Bacterial / genetics
  • RNA, Messenger / metabolism
  • RNA, Ribosomal, 16S / genetics
  • Skin / immunology
  • Skin / microbiology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Allergens
  • Cytokines
  • RNA, Bacterial
  • RNA, Messenger
  • RNA, Ribosomal, 16S
  • Ovalbumin