Bacillus Calmette-Guérin-Induced Human Mast Cell Activation Relies on IL-33 Priming.

Bacillus Calmette-Guérin-Induced Human Mast Cell Activation Relies on IL-33 Priming.
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DOI:
10.3390/ijms23147549
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发表时间:
2022-07-07
影响因子:
5.6
通讯作者:
--
中科院分区:
生物学2区
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卡介苗(BCG)是一种牛分枝杆菌减毒株,对结核病(TB)的保护作用较弱。肥大细胞(MC)在战略上是组织驻留的免疫细胞,是抵御病原体威胁的第一道防线。在本研究中,我们研究了人肾小球系膜细胞(HMC)对卡介苗的反应。我们发现,暴露在卡介苗中的幼稚的HMCs不分泌细胞因子,不脱颗粒,也不支持细菌的摄取和细胞内生长。由于我们可以证明在HMCS中,IL-33促进宿主-病原体相互作用、细胞黏附和激活基因的转录,所以我们使用IL-33作为细胞启动因子。在卡介苗刺激前用IL-33处理HMC,但不用干扰素-γ处理,可增加IL-8、MCP-1和IL-13的分泌,并诱导分枝杆菌结合受体CD48的表达增强。这些效应与重组结核分枝杆菌(Mtb)19-KDa脂蛋白的作用相当。IL-33刺激HMCs可增加MC-BCG的相互作用。因此,我们认为IL-33可能通过致敏HMCs来提高卡介苗的免疫原性。
Bacillus Calmette–Guérin (BCG) vaccine is an attenuated strain of Mycobacterium bovis that provides weak protection against tuberculosis (TB). Mast cells (MCs) are tissue-resident immune cells strategically that serve as the first line of defence against pathogenic threats. In this study, we investigated the response of human MCs (hMCs) to BCG. We found that naïve hMCs exposed to BCG did not secrete cytokines, degranulate, or support the uptake and intracellular growth of bacteria. Since we could show that in hMCs IL-33 promotes the transcription of host-pathogen interaction, cell adhesion and activation genes, we used IL-33 for cell priming. The treatment of hMCs with IL-33, but not IFN-γ, before BCG stimulation increased IL-8, MCP-1 and IL-13 secretion, and induced an enhanced expression of the mycobacteria-binding receptor CD48. These effects were comparable to those caused by the recombinant Mycobacterium tuberculosis (Mtb) 19-KDa lipoprotein. Finally, stimulation of hMCs with IL-33 incremented MC-BCG interactions. Thus, we propose that IL-33 may improve the immunogenicity of BCG vaccine by sensitising hMCs.
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