Antigen presenting cells (APCs), such as classical dendritic cells (DCs) and monocyte-derived DCs (moDCs), activate effector/memory Th2 cells at the airways to drive allergic asthma. We sought to better understand the identification and role of APCs in the lung. To distinguish between classical DCs and moDCs in allergic airway disease, it was shown that the MAR-1 monoclonal antibody, which recognizes mouse FcεRIα, stained moDCs but not classical DCs, suggesting that moDCs uniquely express FcεRI. Surprisingly, we found that moDCs stained with MAR-1 in FcεRIα–/– mice, indicating that MAR-1 binds other molecule(s). Ectopic expression of mouse Fc receptors in a human cell line revealed that MAR-1 antibody cross-reacts with FcγRI (CD64) and FcγRIV. We conclude that the MAR-1 staining on moDCs reflects the expression of FcγRI, rather than FcεRI, similar to tissue macrophages.
We also examined how antigen capture by APCs located near the airways in the steady state leads to the activation of Th2 inflammation upon allergen re-exposure. DCs were thought to be necessary for allergic airway recall responses, yet paradoxically, DCs did not appear to capture antigen at the conducting airways in microscopy studies. We tested whether DCs were necessary to induce allergic lung inflammation after sensitization, by selectively depleting classical DCs using Zbtb46-DTR mice. Unexpectedly, mice depleted of DCs during allergen re-exposure exhibited robust inflammation, indicating that alternative APCs are capable of driving local Th2 responses. Examination of airway proximal regions by microscopy showed that antigen was predominantly captured by CX3CR1-GFP+ cells that expressed MHC-II as well as macrophage markers. Because of their enrichment around the airways, we termed these cells Bronchus-Associated Macrophages (BAMs). BAMs were highly dendritic in morphology but were less motile than DCs and did not migrate to the lymph nodes, making them ideal candidates to serve as tissue-resident APCs at the airways. We found that BAMs presented antigen, activated T cells in culture, and interacted with T cells recruited to the airways in a model of allergic asthma. These observations establish BAMs as local APCs residing around the airways that are capable of promoting allergic airway inflammation.