Journal
JOURNAL OF IMMUNOLOGY
Volume 196, Issue 11, Pages 4498-4509Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1600071
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Funding
- Swedish International Development Agency/Department of Research Cooperation (SAREC)
- Swedish Governmental Agency for Innovation Systems (Vinnova)
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Swedish Foundation for Strategic Research
- Swedish Society for Medical Research
- Karolinska Institutet
- Ake Wiberg Foundation
- Tore Nilsson Foundation
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Every breath we take contains potentially harmful pathogens or allergens. Dendritic cells (DCs), monocytes, and macrophages are essential in maintaining a delicate balance of initiating immunity without causing collateral damage to the lungs because of an exaggerated inflammatory response. To document the diversity of lung mononuclear phagocytes at steady-state, we performed bronchoscopies on 20 healthy subjects, sampling the proximal and distal airways (bronchial wash and bronchoalveolar lavage, respectively), as well as mucosal tissue (endobronchial biopsies). In addition to a substantial population of alveolar macrophages, we identified subpopulations of monocytes, myeloid DCs (MDCs), and plasmacytoid DCs in the lung mucosa. Intermediate monocytes and MDCs were highly frequent in the airways compared with peripheral blood. Strikingly, the density of mononuclear phagocytes increased upon descending the airways. Monocytes from blood and airways produced 10-fold more proinflammatory cytokines than MDCs upon ex vivo stimulation. However, airway monocytes were less inflammatory than blood monocytes, suggesting a more tolerant nature. The findings of this study establish how to identify human lung mononuclear phagocytes and how they function in normal conditions, so that dysregulations in patients with respiratory diseases can be detected to elucidate their contribution to immunity or pathogenesis.
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