Bronchus-associated macrophages efficiently capture and present soluble inhaled antigens and are capable of local Th2 cell activation

Abstract

In allergic asthma, allergen inhalation leads to local Th2 cell activation and peribronchial inflammation. However, the mechanisms for local antigen capture and presentation remain unclear. By two-photon microscopy of the mouse lung, we established that soluble antigens in the bronchial airway lumen were efficiently captured and presented by a population of CD11c+ interstitial macrophages with high CX3CR1-GFP and MHC class II expression. We refer to these cells as Bronchus-Associated Macrophages (BAMs) based on their localization underneath the bronchial epithelium. BAMs were enriched in collagen-rich regions near some airway branchpoints, where inhaled antigens are likely to deposit. BAMs engaged in extended interactions with effector Th2 cells and promoted Th2 cytokine production. BAMs were also often in contact with dendritic cells (DCs). After exposure to inflammatory stimuli, DCs migrated to draining lymph nodes, whereas BAMs remained lung resident. We propose that BAMs act as local antigen presenting cells in the lung and also transfer antigen to DCs.

A human model of asthma exacerbation reveals transcriptional programs and cell circuits specific to allergic asthma

“…Mac1 ( FABP4 ) and quiesMacs (defined by overall lower gene expression) were enriched for canonical Macs ( MARCO , MSR1 , and VSIG4 ) and lipid metabolism genes ( FABP4 and APOE ), consistent with previously described luminal Macs ( 16 , 25 , 51 ). Mac2 ( A2M ) had high expression of complement family genes ( C1QA , C1QB and C1QC ) and lower relative expression of canonical Mac markers, reminiscent of airway-associated Macs (AAMs) recently characterized in mice ( 57 , 58 ).…”

“…moMacs after 21 days in coculture acquired a transcriptional profile similar to that of Mac2 ( A2M ) and were highly enriched for complement genes ( C1QA , C1QB , and C1QC ) and MERTK . Murine AAMs, which are transcriptionally similar to Mac2 ( A2M ), are replenished by CCR2 + monocytes, integrate in the airway epithelium, and exhibit dendriform morphology ( 57 , 58 ). We therefore performed immunofluorescence staining of day 21 cocultures and confirmed that these cells colocalize with the epithelial basal layer, acquire dendritic projections, and express C1Q and MERTK (Fig.…”

“…5, A to C, and fig. S4, A and B) (49)(50)(51)(52)(53)(54)(55)(56)(57)(58). DC subsets included DC1 (CLEC9A), DC2 (CD1C), migratory DCs (migDCs; CCR7), plasmacytoid DCs (pDCs; TCF4), and Axl-Siglec6 DCs (AXL).…”

Comprehensive analysis of lung macrophages and dendritic cells in two murine models of allergic airway inflammation reveals model- and subset-specific accumulation and phenotypic alterations

“…However, clearly more detailed analyses will be needed to further explore on this issue und clarify its relevance in the differences observed between OVA- and HDM-AAI. Further, resident macrophages associated to the bronchi (BAM) have recently been described to capture and present antigens and activate Th2 cells in the lung ( 40 ). These BAM are CD11c + IM characterized by high CX3CR1 and MHCII expression.…”

Initiation of type 2 immunity at barrier surfaces

“…Th2s provide concomitant support for ILC2s in the form of IL-2 144 , solidifying the mutualistic relationship between these cell types within the tissues. An interesting preprint recently found bronchus-associated macrophages interact with effector Th2s in the lung and enhance effector cytokine production from T cells in vitro 165 . Basophils have also been implicated in supporting Th2 responses in the tissues.…”