Cholinergic Pathway Suppresses Pulmonary Innate Immunity Facilitating Pneumonia After Stroke

Odilo Engel, Levent Akyüz, Andrey C da Costa Goncalves, Katarzyna Winek, Claudia Dames, Mareike Thielke, Susanne Herold, Chotima Böttcher, Josef Priller, Hans Dieter Volk, Ulrich Dirnagl, Christian Meisel, Andreas Meisel

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND AND PURPOSE: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive.

METHODS: The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression. We used heart rate variability measurement by telemetry, vagotomy, α7 nicotinic acetylcholine receptor-deficient mice, and parasympathomimetics (nicotine, PNU282987) to measure and modulate parasympathetic activity.

RESULTS: Here, we demonstrate a rapidly increased parasympathetic activity in mice after experimental stroke. Inhibition of cholinergic signaling by either vagotomy or by using α7 nicotinic acetylcholine receptor-deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of α7 nicotinic acetylcholine receptor on different lung cells using bone marrow chimeric mice and isolated primary cells indicated that not only macrophages but also alveolar epithelial cells are a major cellular target of cholinergic anti-inflammatory signaling in the lung.

CONCLUSIONS: Thus, cholinergic pathways play a pivotal role in the development of pulmonary infections after acute central nervous system injury.

Original languageEnglish
Pages (from-to)3232-40
Number of pages9
JournalStroke
Volume46
Issue number11
Early online date8 Oct 2015
DOIs
Publication statusE-pub ahead of print - 8 Oct 2015

Keywords

  • Animals
  • Benzamides
  • Bridged Bicyclo Compounds
  • Bronchoalveolar Lavage Fluid
  • Disease Models, Animal
  • Heart Rate
  • Immunity, Innate
  • Infarction, Middle Cerebral Artery
  • Lung
  • Macrophages, Alveolar
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nicotine
  • Nicotinic Agonists
  • Parasympathetic Nervous System
  • Parasympathomimetics
  • Pneumonia
  • Receptors, Nicotinic
  • Respiratory Mucosa
  • Signal Transduction
  • Stroke
  • Vagotomy
  • Journal Article
  • Research Support, Non-U.S. Gov't

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