期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 55, 期 6, 页码 899-908出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2016-0122OC
关键词
bronchoalveolar lavage; alveolar macrophages; tuberculosis; macaques; human subjects
资金
- National Institutes of Health National Heart, Lung, and Blood Institute [RO1-HL106798, RO1-HL106804, RO1 HL106800]
- Bill and Melinda Gates Foundation
- Otis Foundation for Tuberculosis/PNC Trust
- NIH from the National Center for Research Resources [UL1 RR024989]
- [RO1 AI111871]
- [RO1 HL111523]
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. Inmacaques, 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.
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