Differential regulation of C5a receptor 1 in innate immune cells during the allergic asthma effector phase

PLoS One. 2017 Feb 23;12(2):e0172446. doi: 10.1371/journal.pone.0172446. eCollection 2017.

Abstract

C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma. C5aR1 reporter and wildtype mice developed a similar allergic phenotype with comparable airway resistance, mucus production, eosinophilic/neutrophilic airway inflammation and Th2/Th17 cytokine production. During the allergic effector phase, C5aR1 expression increased in lung tissue eosinophils but decreased in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs) and monocyte-derived DCs (moDCs). Surprisingly, expression in neutrophils was not affected. Of note, moDCs but not CD11b+ cDCs from mediastinal lymph nodes (mLN) expressed less C5aR1 than DCs residing in the lung after OVA challenge. Finally, neither CD103+ cDCs nor cells of the lymphoid lineage such as Th2 or Th17-differentiated CD4+ T cells, B cells or type 2 innate lymphoid cells (ILC2) expressed C5aR1 under allergic conditions. Our findings demonstrate a complex regulation pattern of C5aR1 in the airways, lung tissue and mLN of mice, suggesting that the C5a/C5aR1 axis controls airway constriction and inflammation through activation of myeloid cells in all three compartments in an experimental model of allergic asthma.

MeSH terms

  • Animals
  • Asthma / immunology*
  • Asthma / pathology
  • CD11b Antigen / analysis
  • CD11b Antigen / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Eosinophils / immunology
  • Eosinophils / pathology
  • Immunity, Cellular
  • Lung / immunology*
  • Lung / pathology
  • Macrophages / immunology
  • Macrophages / pathology
  • Mediastinum / pathology
  • Mice
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • Ovalbumin / immunology
  • Receptor, Anaphylatoxin C5a / analysis
  • Receptor, Anaphylatoxin C5a / immunology*

Substances

  • C5ar1 protein, mouse
  • CD11b Antigen
  • Receptor, Anaphylatoxin C5a
  • Ovalbumin

Grants and funding

This work was supported by Deutsche Forschungsgemeinschaft grant KO1245/1 to J.K.; Deutsche Forschungsgemeinschaft grant IRTG 1911/A1 to Y.L., P.K.; and Deutsche Forschungsgemeinschaft grant IRTG 1911/A2 to P.K. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.