关键词: HIV PDL-1 blood neutrophil sputum tuberculosis

Mesh : Humans Neutrophils / immunology Male Adult Female HIV Infections / immunology Immunophenotyping Tuberculosis, Pulmonary / immunology pathology South Africa Coinfection / immunology Middle Aged Phenotype Flow Cytometry Young Adult Mycobacterium tuberculosis / immunology

来  源:   DOI:10.3389/fimmu.2024.1422836   PDF(Pubmed)

Abstract:
UNASSIGNED: Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease.
UNASSIGNED: To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa.
UNASSIGNED: Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1.
UNASSIGNED: Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis.
摘要:
中性粒细胞在结核病的免疫病理学中起着复杂而重要的作用。数据表明,它们在早期感染期间具有保护性,但如果感染发展为活动性疾病,它们将成为免疫病理学的主要驱动因素。中性粒细胞现在被认为存在于功能不同的状态,但是关于中性粒细胞状态或亚群在TB疾病中如何偏斜的研究还很少。
为了解决这个问题,我们通过流式细胞术对德班招募的有或没有HIV合并感染的活动性肺结核患者的血液和气道中的嗜中性粒细胞进行了全面的表型分析,南非。
活动性结核病与血液中嗜中性粒细胞向与激活和凋亡相关的表型的严重偏斜有关,减少吞噬作用,反向迁移,和免疫调节。这种偏斜显然也在气道中性粒细胞中,特别是表达PDL-1和LOX-1的调节亚群。HIV共感染不会影响血液中的中性粒细胞亚群,但与气道表型变化以及关键中性粒细胞功能蛋白cathelicidin和精氨酸酶1的减少有关。
活动性结核病与血液和气道中性粒细胞的严重偏斜有关,并提示中性粒细胞可能加剧结核病免疫病理学的多种机制。这些数据表明在诊断时减少嗜中性粒细胞介导的肺病理学的潜在途径。
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