科学家揭示麻风肉芽肿抗菌反应网络的细胞结构
2021-06-28   阅读:297   来源:自然

美国加州大学洛杉矶分校Robert L. Modlin团队在研究中取得进展。他们的最新研究揭示了人麻风肉芽肿抗菌反应网络的细胞结构。相关论文于2021年6月24日发表于国际学术期刊《自然-免疫学》杂志。

在本研究中,研究人员利用单细胞和空间测序对麻风活检标本进行了检测,揭示了与人麻风肉芽肿抗菌反应相关的单细胞表型。研究人员主要探究了动态逆转反应 (RRs),该过程会使一些播散性瘤性麻风(l-lep)患者转变为自限结核性麻风 (T-lep),并产生有效的抗菌反应。

研究鉴定了一组参与抗菌反应的蛋白编码基因,这些蛋白质在RR与L-lep病变中差异表达,并受干扰素-γ和白细胞介素-1β的调节。通过整合RR和T-lep病变中关键细胞类型和抗菌基因表达的空间分布,研究人员描绘了其网络图谱,揭示了肉芽肿的组织结构、巨噬细胞、T细胞、角质形成细胞和成纤维细胞各自的产生抗菌反应的组分。

据介绍,肉芽肿具有复杂的细胞结构,该细胞结构主要由巨噬细胞和淋巴细胞组成,其功能是遏制和杀死入侵的病原体。

附:英文原文

Title: The cellular architecture of the antimicrobial response network in human leprosy granulomas

Author: Feiyang Ma, Travis K. Hughes, Rosane M. B. Teles, Priscila R. Andrade, Bruno J. de Andrade Silva, Olesya Plazyo, Lam C. Tsoi, Tran Do, Marc H. Wadsworth, Aislyn Oulee, Maria Teresa Ochoa, Euzenir N. Sarno, M. Luisa Iruela-Arispe, Eynav Klechevsky, Bryan Bryson, Alex K. Shalek, Barry R. Bloom, Johann E. Gudjonsson, Matteo Pellegrini, Robert L. Modlin

Issue&Volume: 2021-06-24

Abstract: Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1β. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.

DOI: 10.1038/s41590-021-00956-8

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