Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation

Clin Exp Allergy. 2022 Apr;52(4):518-529. doi: 10.1111/cea.14077. Epub 2021 Dec 16.

Abstract

Background: Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti-asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation.

Methods: Six-week-old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH-S) treated with or without A. lwoffii before IL-13 stimulation were analysed by quantitative RT-PCR.

Results: In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+ M2a and CD11b+ M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+ M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down-regulated the expression of M2 markers related but up-regulated those related to M2b macrophages.

Conclusions and clinical relevance: Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.

Keywords: Acinetobacter lwoffii; airway hyperresponsiveness; asthma; macrophage activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter
  • Animals
  • Asthma*
  • Bronchoalveolar Lavage Fluid
  • Disease Models, Animal
  • Female
  • Humans
  • Immunity, Innate
  • Inflammation
  • Lung
  • Lymphocytes / metabolism
  • Macrophage Activation*
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin

Substances

  • Ovalbumin

Supplementary concepts

  • Acinetobacter lwoffii