Innate immune network in asthma: studies on dendritic cell interaction with airway epithelium

Background: The interaction of various types of innate and adaptive immune cells during ongoing allergic asthma is pivotal for the outcome and the resolution of the disease. Dendritic cells (DC) are key regulators of this network, however, the airway epithelium is the first entry site for airborne allergens and signals derived from these cells can affect DC function decisively.

Methods: A 3D co-culture model involving the airway epithelial cell line Calu-3, cultured under air-liquid interface (ALI) conditions, and monocyte-derived DC was used to study the interaction of these cell types when challenged with airborne allergens. In addition, we monitored changes in cell morphology with a real-time cell analyzer (RTCA).

Results: Stimulation of Calu-3 cells with the allergens Der p1, Der p 2 and Bet v1 resulted in minor activation of these epithelial cells whilst allergen-treatment of DC led to differential induction of immune stimulatory cytokines such as IL-6, CXCL8 and CCL22. In contrast to the stimulation of the individual cell types, we observed further changes in cytokine induction under ALI co-culture conditions. These were already detected under conditions where direct epithelium/DC contact was prevented but it was at maximum when contact was enabled, indicating the importance of soluble factors in addition to direct cell interaction. Furthermore, using the RTCA we see a modification of Calu-3 morphology when challenged with Bet v1 only in the presence of DC.

Conclusion: The establishment of cell culture systems that enable allergen challenge studies on DC/airway epithelial cell co-cultures underline the importance of the direct cell contact in this context and will provide further insights into the nature of the DC-epithelium interplay.