Calcium Dynamics Regulate Protective Responses and Growth of Staphylococcus aureus in Macrophages.

Q2 Biochemistry, Genetics and Molecular Biology Biomolecular Concepts Pub Date : 2020-12-31 DOI:10.1515/bmc-2020-0021
Chaitenya Verma, Kumar Rana Ankush, Vandana Anang, Brijendra K Tiwari, Aayushi Singh, Shakuntala Surender Kumar Saraswati, Malini Shariff, Krishnamurthy Natarajan
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引用次数: 2

Abstract

Staphylococcus aureus (S. aureus) is a gram-positive bacteria, which causes various fatal respiratory infections including pneumonia. The emergence of Methicillin-Resistance Staphylococcus aureus (MRSA) demands a thorough understanding of host-pathogen interactions. Here we report the role of calcium in regulating defence responses of S. aureus in macrophages. Regulating calcium fluxes in cells by different routes differentially governs the expression of T cell costimulatory molecule CD80 and Th1 promoting IL-12 receptor. Inhibiting calcium influx from extracellular medium increased expression of IFN-γ and IL-10 while blocking calcium release from the intracellular stores inhibited TGF-β levels. Blocking voltage-gated calcium channels (VGCC) inhibited the expression of multiple cytokines. While VGCC regulated the expression of apoptosis protein Bax, extracellular calcium-regulated the expression of Cytochrome-C. Similarly, VGCC regulated the expression of autophagy initiator Beclin-1. Blocking VGCC or calcium release from intracellular stores promoted phagosome-lysosome fusion, while activating VGCC inhibited phagosomelysosome fusion. Finally, calcium homeostasis regulated intracellular growth of Staphylococcus, although using different mechanisms. While blocking extracellular calcium influx seems to rely on IFN-γ and IL-12Rβ receptor mediated reduction in bacterial survival, blocking either intracellular calcium release or via VGCC route seem to rely on enhanced autophagy mediated reduction of intracellular bacterial survival. These results point to fine-tuning of defence responses by routes of calcium homeostasis.

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钙动力学调节巨噬细胞的保护反应和金黄色葡萄球菌的生长。
金黄色葡萄球菌(金黄色葡萄球菌)是一种革兰氏阳性细菌,可引起各种致命的呼吸道感染,包括肺炎。耐甲氧西林金黄色葡萄球菌(MRSA)的出现要求对宿主-病原体相互作用有透彻的了解。在这里,我们报告了钙在巨噬细胞中调节金黄色葡萄球菌防御反应中的作用。不同途径调节细胞钙通量对T细胞共刺激分子CD80和促IL-12受体Th1的表达有不同的调控作用。抑制细胞外钙内流可增加IFN-γ和IL-10的表达,而阻断细胞内钙的释放可抑制TGF-β水平。阻断电压门控钙通道(VGCC)抑制多种细胞因子的表达。VGCC调控凋亡蛋白Bax的表达,胞外钙调控细胞色素c的表达。同样,VGCC调节自噬启动物Beclin-1的表达。阻断VGCC或细胞内储存的钙释放促进吞噬体-溶酶体融合,而激活VGCC则抑制吞噬体-溶酶体融合。最后,钙稳态调节葡萄球菌的细胞内生长,尽管使用不同的机制。虽然阻断细胞外钙内流似乎依赖于IFN-γ和IL-12Rβ受体介导的细菌存活减少,但阻断细胞内钙释放或通过VGCC途径似乎依赖于增强的自噬介导的细胞内细菌存活减少。这些结果指出,通过钙稳态的途径微调防御反应。
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来源期刊
Biomolecular Concepts
Biomolecular Concepts Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
5.30
自引率
0.00%
发文量
27
审稿时长
12 weeks
期刊介绍: BioMolecular Concepts is a peer-reviewed open access journal fostering the integration of different fields of biomolecular research. The journal aims to provide expert summaries from prominent researchers, and conclusive extensions of research data leading to new and original, testable hypotheses. Aspects of research that can promote related fields, and lead to novel insight into biological mechanisms or potential medical applications are of special interest. Original research articles reporting new data of broad significance are also welcome. Topics: -cellular and molecular biology- genetics and epigenetics- biochemistry- structural biology- neurosciences- developmental biology- molecular medicine- pharmacology- microbiology- plant biology and biotechnology.
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