title: Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.
abstract: The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. Six subsets of phagocytic APC (HLA-DR+) were consistently observed. Aside from alveolar macrophages, subsets of Langerin+, BDCA1-CD14+, BDCA1+CD14+, BDCA1+CD14-, and BDCA1-CD14-cells were identified. These subsets varied in their ability to internalize Escherichia coli, Staphylococcus aureus, and Bacillus anthracis particles. All subsets were more efficient at internalizing S. aureus and B. anthracis compared with E. coli Alveolar macrophages and CD14+cells were overall more efficient at particle internalization compared with the four other populations. Subsets were further separated into two groups based on their inherent capacities to upregulate surface CD83, CD86, and CCR7 expression levels. Whole-genome transcriptional profiling revealed a clade of "true dendritic cells" consisting of Langerin+, BDCA1+CD14+, and BDCA1+CD14-cells. The dendritic cell clade was distinct from a macrophage/monocyte clade, as supported by higher mRNA expression levels of several dendritic cell-associated genes, including CD1, FLT3, CX3CR1, and CCR6 Each clade, and each member of both clades, was discerned by specific upregulated genes, which can serve as markers for future studies in healthy and diseased states.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.|Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Vineet I
authors.initials: VI
authors.lastname: Patel
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: J Leland
authors.initials: JL
authors.lastname: Booth
authors.affiliation: Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Duggan
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Steven
authors.initials: S
authors.lastname: Cate
authors.affiliation: Office of Aviation Medicine, Federal Aviation Administration, Oklahoma City, OK 73169.
authors.forename: Vicky L
authors.initials: VL
authors.lastname: White
authors.affiliation: Cherokee Healthcare Services, Catoosa, OK 74015.
authors.forename: David
authors.initials: D
authors.lastname: Hutchings
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.|Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; and.
authors.forename: Susan
authors.identifier: 0000-0001-5479-9952
authors.initials: S
authors.lastname: Kovats
authors.affiliation: Office of Aviation Medicine, Federal Aviation Administration, Oklahoma City, OK 73169.
authors.forename: Dennis M
authors.identifier: 0000-0002-2664-4360
authors.initials: DM
authors.lastname: Burian
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298.
authors.forename: Mikhail
authors.identifier: 0000-0002-0086-8358
authors.initials: M
authors.lastname: Dozmorov
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; jordan-metcalf@ouhsc.edu.|Pulmonary and Critical Care Division, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Metcalf
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000145:classification / Q000502:physiology*; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000145:classification / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D051940:B7-2 Antigen; D006023:Glycoproteins; D007136:Immunoglobulins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C437944:CD1C protein, human