代谢活跃的嗜中性粒细胞是结核分枝杆菌的容许生态位。

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-10-01 DOI:10.1016/j.mucimm.2024.05.007
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引用次数: 0

摘要

结核分枝杆菌(Mtb)感染的中性粒细胞经常出现在活动性结核病(TB)患者的呼吸道中,肺部中性粒细胞的过度募集与结核病的细菌负荷增加和病理恶化有关。中性粒细胞对 Mtb 的容许性以及在结核病中致病的能力一直难以捉摸。在这里,我们确定了中性粒细胞的代谢和功能特征,这些特征有助于它们在 Mtb 感染中的致病性。通过单细胞代谢和转录分析,我们发现受 Mtb 感染的肺部中性粒细胞线粒体代谢升高,这主要归因于诱导了代谢活性增强的活化中性粒细胞。在Mtb感染的非人灵长类肺肉芽肿中也发现了活化的中性粒细胞亚群。从功能上讲,活化的中性粒细胞可包藏更多有活力的细菌,并显示出更强的脂质摄取和积累能力。令人惊讶的是,我们发现 IFNγ 在 Mtb 感染期间促进了肺中性粒细胞的活化。最后,对脂质摄取途径的干扰选择性地损害了Mtb在活化的中性粒细胞中的存活。这些研究结果表明,中性粒细胞的异质性和代谢多样性是它们对Mtb的容许性的关键,中性粒细胞中的代谢途径是结核病的潜在宿主导向疗法。
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Metabolically active neutrophils represent a permissive niche for Mycobacterium tuberculosis
Mycobacterium tuberculosis (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils with enhanced metabolic activities. The activated neutrophil subpopulation was also identified in the lung granulomas from Mtb-infected non-human primates. Functionally, activated neutrophils harbored more viable bacteria and displayed enhanced lipid uptake and accumulation. Surprisingly, we found that interferon-γ promoted the activation of lung neutrophils during Mtb infection. Lastly, perturbation of lipid uptake pathways selectively compromised Mtb survival in activated neutrophils. These findings suggest that neutrophil heterogeneity and metabolic diversity are key to their permissiveness for Mtb and that metabolic pathways in neutrophils represent potential host-directed therapeutics in TB.
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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