Allergic airway inflammation induces the migration of dendritic cells into airway sensory ganglia

Abstract

BackgroundA neuroimmune crosstalk between dendritic cells (DCs) and airway nerves in the lung has recently been reported. However, the presence of DCs in airway sensory ganglia under normal and allergic conditions has not been explored so far. Therefore, this study aims to investigate the localisation, distribution and proliferation of DCs in airway sensory ganglia under allergic airway inflammation.MethodsUsing the house dust mite (HDM) model for allergic airway inflammation BALB/c mice were exposed to HDM extract intranasally (25 μg/50 μl) for 5 consecutive days a week over 7 weeks. With the help of the immunohistochemistry, vagal jugular-nodose ganglia complex (JNC) sections were analysed regarding their expression of DC-markers (MHC II, CD11c, CD103), the neuronal marker PGP 9.5 and the neuropeptide calcitonin gene-related peptide (CGRP) and glutamine synthetase (GS) as a marker for satellite glia cells (SGCs). To address the original source of DCs in sensory ganglia, a proliferation experiment was also carried in this study.ResultsImmune cells with characteristic DC-phenotype were found to be closely located to SGCs and vagal sensory neurons under physiological conditions. The percentage of DCs in relation to neurons was significantly increased by allergic airway inflammation in comparison to the controls (HDM 51.38 ± 2.38% vs. control 28.16 ± 2.86%, p < 0.001). The present study also demonstrated that DCs were shown to proliferate in jugular-nodose ganglia, however, the proliferation rate of DCs is not significantly changed in the two treated animal groups (proliferating DCs/ total DCs: HDM 0.89 ± 0.38%, vs. control 1.19 ± 0.54%, p = 0.68). Also, increased number of CGRP-positive neurons was found in JNC after allergic sensitisation and challenge (HDM 31.16 ± 5.41% vs. control 7.16 ± 1.53%, p < 0.001).ConclusionThe present findings suggest that DCs may migrate from outside into the ganglia to interact with sensory neurons enhancing or protecting the allergic airway inflammation. The increase of DCs as well as CGRP-positive neurons in airway ganglia by allergic airway inflammation indicate that intraganglionic DCs and neurons expressing CGRP may contribute to the pathogenesis of bronchial asthma. To understand this neuroimmune interaction in allergic airway inflammation further functional experiments should be carried out in future studies.

Steroid Treatment Reduces Allergic Airway Inflammation and Does Not Alter the Increased Numbers of Dendritic Cells and Calcitonin Gene-Related Peptide-Expressing Neurons in Airway Sensory Ganglia

“…Recently, an increase in the number of DC and CGRP-expressing neurons in the JNC caused by HDM-induced allergic airway inflammation was found. These findings suggest that CGRP may contribute to the migration of immune cells such as DC into airway sensory ganglia and to enhance or suppress airway inflammation [4,30]. In correspondence with our previous results, DC and CGRP-expressing neurons in the JNC were enhanced after treatment with HDM.…”

“…The application of house dust mites (HDM) to induce chronic allergic airway inflammation has been reported previously [4]. Shortly, BALB/c mice (n = 6) were exposed consecutively 5 days a week for a total of 7 weeks to intranasal (i.n.)…”

“…The immunofluorescence staining has been described previously [4]. Briefly, every fourth section from serial sections of JNC was dried at room temperature for 15 min and then rehydrated for 5 min in PBS.…”

“…In our previous study, DC were found to be localized in the jugular-nodose ganglion complex (JNC) under physiologic conditions, and their number was significantly increased during allergic airway inflammation by migration from outside into the ganglia [4]. However, the impact of FP on neuropeptide expression and on the migration of DC in airway sensory ganglia has been not explored so far.…”

“…As antigen-presenting and phagocytic cells, DC are known to play a key role in the allergic immune response and to be localized in many organs like the skin, the mucosa of the intestines, and the lungs [2,3,4,5]. …”