颗粒菌素抗菌活性促进结核分枝杆菌休眠。

IF 3.7 3区 医学 Q2 IMMUNOLOGY
Sarah Schmidiger, Erin F McCaffrey, Jan M Schmidt, Owais Abdul Hameed, Max Mpina, Anneth Tumbo, Elirehema Mfinanga, Frederick Haraka, Hellen Hiza, Mohamed Sasamalo, Jerry Hella, Michael Walch, Jacques Fellay, Sébastien Gagneux, Klaus Reither, José M Carballido, Ainhoa Arbués, Damien Portevin
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引用次数: 0

摘要

由结核分枝杆菌(Mtb)引起的人类结核病(TB)仍然是全球公共卫生威胁。肉芽肿是结核发病机制的一个标志,它可以清除、控制或加剧感染。结核分枝杆菌利用围护作为藏身之处,持续处于休眠状态,耐抗生素状态,只有在免疫抑制时才会复苏。肉芽肿反应驱动结核持续性的免疫决定因素仍然难以捉摸。在此,我们从结核病患者的外周血单个核细胞标本中生成离体肉芽肿样结构,并应用高维质量细胞术来阐明促使结核杆菌休眠的免疫因素。与健康对照相比,患者来源的标本迅速迫使结核分枝杆菌在体外变成休眠样。这一观察结果与活化的先天(类)细胞毒性淋巴细胞的富集有关,并且需要CD56+淋巴细胞的存在,或者更具体地说,需要其颗粒的含量。最后,我们证明了直接暴露于颗粒蛋白酶诱导结核分枝杆菌休眠,从而揭示了细胞毒性淋巴细胞活性的免疫逃逸机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.

Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.

Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.

Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.

Human tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a global public health threat. Granulomas constitute a hallmark of TB pathogenesis that can clear, contain, or exacerbate an infection. Containment is exploited by Mtb as a hideout to persist in a dormant, antibiotic-tolerant state, only to resuscitate upon immunosuppression. The immune determinants of a granulomatous response driving Mtb persistence remain elusive. We here generated ex vivo granuloma-like structures from peripheral blood mononuclear cell specimens of TB patients and applied high-dimensional mass cytometry to elucidate immune factors prompting Mtb dormancy. Compared with healthy controls, patient-derived specimens rapidly forced Mtb to become dormant-like ex vivo. This observation correlated with an enrichment in activated, innate (-like) cytotoxic lymphocytes and required the presence of CD56+ lymphocytes or, more specifically, the content of their granules. Finally, we demonstrated that direct exposure to granulysin induces Mtb dormancy, thereby unravelling an immune escape mechanism to cytotoxic lymphocyte activity.

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来源期刊
CiteScore
8.30
自引率
3.70%
发文量
224
审稿时长
2 months
期刊介绍: The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.
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