Selected β-Glucans Act as Immune-Training Agents by Improving Anti-Mycobacterial Activity in Human Macrophages: A Pilot Study.

IF 4.7 3区 医学 Q2 IMMUNOLOGY Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-21 DOI:10.1159/000533873
Clara Braian, Lovisa Karlsson, Jyotirmoy Das, Maria Lerm
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Abstract

Epigenetic reprogramming of innate immune cells by β-glucan in a process called trained immunity leads to an enhanced host response to a secondary infection. β-Glucans are structural components of plants, algae, fungi, and bacteria and thus recognized as non-self by human macrophages. We selected the β-glucan curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and β-glucan-rich culture supernatant of Alternaria and investigated whether they could produce trained immunity effects leading to an increased control of virulent Mycobacterium tuberculosis. We observed a significant M. tuberculosis growth reduction in macrophages trained with curdlan and Alternaria, which also correlated with increased IL-6 and IL-1β release. WGP dispersible-trained macrophages were stratified into "non-responders" and "responders," according to their ability to control M. tuberculosis, with "responders" producing higher IL-6 levels. The addition of neutrophils to infected macrophage cultures further enhanced macrophage control of virulent M. tuberculosis, but not in a stimuli-dependent manner. Pathway enrichment analysis of DNA methylome data also highlighted hypomethylation of genes in pathways associated with signaling and cellular reorganization and motility, and "responders" to WGP training were enriched in the interferon-gamma signaling pathway. This study adds evidence that certain β-glucans show promise as immune-training agents.

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一项初步研究表明,选定的β-葡聚糖通过提高人体巨噬细胞的抗分枝杆菌活性,起到免疫训练剂的作用。
在一个称为训练免疫的过程中,β-葡聚糖对先天免疫细胞的表观遗传学重新编程,导致宿主对二次感染的反应增强。β-葡聚糖是植物、藻类、真菌和细菌的结构成分,因此被人类巨噬细胞识别为非自身。我们选择了来自粪产碱杆菌的β-葡聚糖凝胶兰、可分散于酿酒酵母的WGP和链格孢菌富含β-葡聚糖的培养上清液,并研究了它们是否能产生训练的免疫效果,从而提高对毒力结核分枝杆菌的控制。我们观察到用curdlan和Alternaria训练的巨噬细胞中结核分枝杆菌的生长显著减少,这也与IL-6和IL-1β释放增加有关。根据WGP可分散训练的巨噬细胞控制结核分枝杆菌的能力,将其分为“无应答者”和“应答者”,其中“有应答者”产生更高的IL-6水平。向受感染的巨噬细胞培养物中添加中性粒细胞进一步增强了巨噬细胞对毒力结核分枝杆菌的控制,但不是以刺激依赖的方式。DNA甲基组数据的通路富集分析还强调了与信号传导、细胞重组和运动相关的通路中基因的低甲基化,并且WGP训练的“应答者”在干扰素-γ信号通路中富集。这项研究进一步证明,某些β-葡聚糖有望成为免疫训练剂。
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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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