Lu Lu, Wei RanLei, Bhakta Sanjib, Waddell Simon J, Boix Ester
College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 610000, China.
Department of Biochemistry and Molecular Biology, Faculty of Biosciences, Universitat Autonoma de Barcelona, 08290 Cerdanyola del Vallès, Spain.
Antibiotics (Basel). 2021 Jan 20;10(2):97. doi: 10.3390/antibiotics10020097.
Tuberculosis (TB) is still a leading cause of death worldwide. Treatments remain unsatisfactory due to an incomplete understanding of the underlying host-pathogen interactions during infection. In the present study, weighted gene co-expression network analysis (WGCNA) was conducted to identify key macrophage modules and hub genes associated with mycobacterial infection. WGCNA was performed combining our own transcriptomic results using -infected human monocytic macrophages (THP1) with publicly accessible datasets obtained from three types of macrophages infected with seven different mycobacterial strains in various one-to-one combinations. A hierarchical clustering tree of 11,533 genes was built from 198 samples, and 47 distinct modules were revealed. We identified a module, consisting of 226 genes, which represented the common response of host macrophages to different mycobacterial infections that showed significant enrichment in innate immune stimulation, bacterial pattern recognition, and leukocyte chemotaxis. Moreover, by network analysis applied to the 74 genes with the best correlation with mycobacteria infection, we identified the top 10 hub-connecting genes: , , , , , , , , and . Interestingly, apart from the well-known Toll-like receptor and inflammation-associated genes, other genes may serve as novel TB diagnosis markers and potential therapeutic targets.
结核病（TB）仍是全球主要的死亡原因。由于对感染期间宿主与病原体相互作用的潜在机制了解不全面，治疗效果仍不尽人意。在本研究中，进行了加权基因共表达网络分析（WGCNA），以鉴定与分枝杆菌感染相关的关键巨噬细胞模块和枢纽基因。结合我们自己使用感染人类单核巨噬细胞（THP1）的转录组结果与从三种巨噬细胞感染七种不同分枝杆菌菌株的各种一对一组合中获得的公开可用数据集，进行了WGCNA。从198个样本构建了11533个基因的层次聚类树，并揭示了47个不同的模块。我们鉴定出一个由226个基因组成的模块，它代表了宿主巨噬细胞对不同分枝杆菌感染的共同反应，在先天免疫刺激、细菌模式识别和白细胞趋化性方面表现出显著富集。此外，通过对与分枝杆菌感染相关性最佳的74个基因进行网络分析，我们鉴定出前10个枢纽连接基因： 、 、 、 、 、 、 、 、 和 。有趣的是，除了众所周知的Toll样受体和炎症相关基因外，其他基因可能作为新型结核病诊断标志物和潜在治疗靶点。
