title: Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection.
abstract: Immune cells of the distal airways serve as "first responders" of host immunity to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (LTBI) to active tuberculosis of various degrees of severity. To further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and cynomolgus macaques before and after Mtb infection. A simple gating strategy effectively defined BAL T-cell and phagocyte populations in both species. BAL from Mtb-naive humans and macaques showed similar differential cell counts. BAL T cells of macaques were composed of fewer CD4+cells but more CD8+and CD4+CD8+double-positive cells than were BAL T cells of humans. The most common mononuclear phagocyte population in BAL of both species displayed coexpression of HLA-DR, CD206, CD11b, and CD11c; however, multiple phagocyte subsets displaying only some of these markers were observed as well. Macaques with LTBI displayed a marked BAL lymphocytosis that was not observed in humans with LTBI. In macaques, the prevalence of specific mononuclear phagocyte subsets in baseline BAL correlated with ultimate outcomes of Mtb infection (i.e., LTBI versus active disease). Overall, these findings demonstrate the comparability of studies of pulmonary immunity to Mtb in humans and macaques. They also indicate a previously undescribed complexity of airway mononuclear phagocyte populations that suggests further lines of investigation relevant to understanding the mechanisms of both protection from and susceptibility to the development of active tuberculosis within the lung.
authors: 1 Division of Pulmonary, Critical Care and Sleep Medicine.|2 The Louis Stokes Cleveland Department of Veterans' Affairs Medical Center.|3 University Hospitals Case Medical Center, and.
authors: Richard F
authors: RF
authors: Silver
authors: 4 Departments of Microbiology and Molecular Genetics and.
authors: Amy J
authors: AJ
authors: Myers
authors: 1 Division of Pulmonary, Critical Care and Sleep Medicine.
authors: Jessica
authors: J
authors: Jarvela
authors: 4 Departments of Microbiology and Molecular Genetics and.
authors: JoAnne
authors: J
authors: Flynn
authors: 5 Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: Tara
authors: T
authors: Rutledge
authors: 6 Pediatric Pulmonology, Allergy and Immunology, Case Western Reserve University School of Medicine, Cleveland, Ohio; and.
authors: Tracey
authors: T
authors: Bonfield
authors: 5 Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: Philana Ling
authors: 0000-0001-5169-3714
authors: PL
authors: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006801:Humans; D055985:Latent Tuberculosis / Q000276:immunology; D007958:Leukocyte Count; D007962:Leukocytes / Q000473:pathology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008252:Macaca fascicularis; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010586:Phagocytes / Q000378:metabolism; D010641:Phenotype; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: alveolar macrophages; bronchoalveolar lavage; human subjects; macaques; tuberculosis