Bronchus-associated macrophages efficiently capture and present soluble inhaled antigens and are capable of local Th2 cell activation
- University of California, San Francisco, United States
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.
Data availability
Relevant data are included in the manuscript figures and examples of 3D visualizations and time-lapse imaging are provided as videos. The RNAseq data have been deposited at the NCBI Gene Expression Omnibus (GEO) and are accessible through GEO Series accession number GSE214177 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE214177)
Article and author information
Author details
Christopher D C Allen
Funding
National Heart, Lung, and Blood Institute (DP2HL117752)
- Xin-Zi Tang
- Cynthia Cho
- Christopher D C Allen
National Institute of Allergy and Infectious Diseases (R21AI130495)
- Xin-Zi Tang
- Cynthia Cho
- Christopher D C Allen
UCSF Cardiovascular Research Institute
- Xin-Zi Tang
- Lieselotte S M Kreuk
- Cynthia Cho
- Christopher D C Allen
UCSF Sandler Asthma Basic Research Center
- Xin-Zi Tang
- Lieselotte S M Kreuk
- Cynthia Cho
- Christopher D C Allen
Agency for Science, Technology and Research
- Xin-Zi Tang
National Institute of Allergy and Infectious Diseases (T32AI007334-31)
- Lieselotte S M Kreuk
UCSF Program for Breakthrough Biomedical Research
- Ross Metzger
- Christopher D C Allen
National Heart, Lung, and Blood Institute (T32HL007731-28)
- Lieselotte S M Kreuk
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The care, maintenance, and experimental manipulation of mice followedguidelines established by the Institutional Animal Care and Use Committee of the University of California, San Francisco under approved protocols AN079036, AN089524, AN111286, AN175836, and AN191685.
Copyright
© 2022, Tang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bronchus-associated macrophages efficiently capture and present soluble inhaled antigens and are capable of local Th2 cell activation
eLife 11:e63296.
https://doi.org/10.7554/eLife.63296
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Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA−CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3−CCR7+Helios−CD127−CD8+) and pro-inflam Macs (CD206−CD163−CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163−CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206− pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.
