Mycobacterium tuberculosis modifies cell wall carbohydrates during biofilm growth with a concomitant reduction in complement activation
Mycobacterium tuberculosis modifies cell wall carbohydrates during biofilm growth with a concomitant reduction in complement activation
复制标题
结核分枝杆菌在生物膜生长过程中改变细胞壁碳水化合物，同时减少补体激活
DOI：
10.1101/2021.03.23.436651
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Keating T
中科院分区：
文献类型：
--
作者：
Keating T
结核病新疫苗的开发需要理解宿主-病原体相互作用的分子和细胞机制以及如何调节免疫反应以实现对疾病的保护。补体协调先天性和适应性免疫应答的许多方面。然而，很少有人知道在结核病的补体途径的贡献，特别是关于分枝杆菌表型。M.在疾病期间，在肉芽肿的非细胞边缘发现结核病，并且这些可能存在于原发性TB发作后的坏死病变中。我们的研究旨在确定哪些分枝杆菌细胞壁成分在生物膜生长过程中发生了变化，以及这些细胞壁变化如何改变补体反应。我们证明了M.结核菌生物膜修饰了它们的细胞壁碳水化合物，并引起经典途径和凝集素途径活化减少。与该发现一致的是生物膜细胞壁碳水化合物提取物上C3 b/iC 3b沉积的减少。在这里，我们强调了细胞壁碳水化合物的变化在生物膜生长ofM的作用。结核病和随后的补体激活调节。
The development of new vaccines for TB needs to be underpinned by an understanding of both the molecular and cellular mechanisms of host-pathogen interactions and how the immune response can be modulated to achieve protection from disease. Complement orchestrates many aspects of the innate and adaptive immune responses. However, little is known about the contribution of the complement pathways during TB disease, particularly with respect to mycobacterial phenotype. Extracellular communities (biofilms) ofM. tuberculosisare found in the acellular rim of granulomas, during disease, and these are likely to be present in post-primary TB episodes, in necrotic lesions. Our study aimed to determine which mycobacterial cell wall components were altered during biofilm growth and how these cell wall alterations modified the complement response. We have shown thatM. tuberculosisbiofilms modified their cell wall carbohydrates and elicited reduced classical and lectin pathway activation. Consistent with this finding was the reduction of C3b/iC3b deposition on biofilm cell wall carbohydrate extracts. Here, we have highlighted the role of cell wall carbohydrate alterations during biofilm growth ofM. tuberculosisand subsequent modulation of complement activation.
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