Aspergillus Fumigatus (Af) Induced Airway Epithelial Accumulation and Decreased Lymph Node Homing of Myeloid Dentritic Cells (DC) in the Lung of Mice with Chronic Granulomatous Disease (CGD)

Lisa R. Forbes, Akshit Gupta, Blerian Kolkalari, Imre Redai, Angela Haczku

Abstract: 

Rationale

The lung of CGD patients and gp91PHOX-/- (CGD) mice is characterized by a hyperinflammatory pulmonary phenotype, destruction of the pulmonary epithelium and granuloma formation, We hypothesized that abnormal proinflammatory myeloid DC accumulation contributes to these changes in the CGD lung.

Methods

The role of CCR4 and CCR7 receptors and their ligands in airway inflammation and DC migration was studied in wild type (WT) and CGD mice sensitized and challenged with Aspergillus fumigatus (Af) 0, 24 and 96h later. Cells from dissociated lung, regional lymph nodes and bronchoalveolar lavage (BAL) were assessed for phenotype, CCR4 and CCR7 expression by FACS analysis and cytokine and chemokine ligand expression by Luminex assay.

Results

Naïve CGD mice had increased numbers of CCR7+ DC in the lung compared to WT mice. Af induced a gradual accumulation of CD11b+CD11c+MHCII+ myeloid DC in the airways of both WT and CGD mice. However, enhanced IL-5 and IL-13 and diminished CCL19 expression in the BAL of CGD mice at 24h was followed by increased CCL17 release and significantly heightened numbers of CCR4+ myeloid DC and eosinophilic granulocytes in comparison with WT mice 96h after Af challenge. Assessment of lymph node homing using intranasal CFSE labeling together with Af, showed decreased proportions of CFSE-labeled CD11c+MHCII+ cells in the thoracic lymph nodes of CGD mice compared to WT mice.

Conclusions

Our results suggest that an increased epithelial and a diminished lymph node homing of proinflammatory, CD11b+CD11c+MHCII+ DC may contribute to the chronic inflammation and granuloma formation in the CGD lung.

Journal of Allergy and Clinical Immunology, Vol. 131, Issue 2, AB128

http://dx.doi.org/10.1016/j.jaci.2012.12.1125

abstract No: 

461
    • AAAAI 2013 (69th)