Bronchus-associated macrophages are positioned for soluble antigen capture from the airway lumen and for local Th2 cell activation

Abstract

AbstractThe aberrant activation of immune responses at barrier surfaces may lead to pathological inflammation. In allergic asthma, allergen inhalation leads to peri-bronchial inflammation and the activation of antigen-specific Th2 cells critical for disease pathogenesis. However, the mechanisms for local allergen capture and antigen presentation remain unclear. By two-photon laser scanning microscopy, we established that soluble antigens that deposited along the bronchial airways were primarily captured and presented by a population of interstitial macrophages with high CX3CR1-GFP and surface MHC class II expression. These cells were strategically positioned underneath the bronchial epithelium and were enriched in collagen-rich regions near some airway branchpoints, where inhaled antigens are likely to deposit. We refer to these cells as Bronchus-Associated Macrophages (BAMs) based on their localization. BAMs efficiently captured, processed, and presented antigen; activated effector Th2 cells; formed extended interactions with T cells in vivo; and remained lung resident after exposure to inflammatory stimuli. In contrast, classical DCs migrated to draining lymph nodes and were not necessary for the induction of allergic lung inflammation in sensitized mice, suggesting that BAMs act as local antigen presenting cells in the lung.