Antibiotics Differentially Modulate Lipoteichoic Acid-Mediated Host Immune Response.
Antibiotics Differentially Modulate Lipoteichoic Acid-Mediated Host Immune Response.
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DOI：
10.3390/antibiotics9090573
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发表时间：
2020-09-03
期刊：
影响因子：
--
通讯作者：
Wong-Beringer A
中科院分区：
文献类型：
--
作者：
Algorri M;Wong-Beringer A
在金黄色葡萄球菌菌血症中，我们的研究小组已经表明，尽管接受了抗生素，但倾向于免疫麻痹表型的促炎和抗炎细胞因子反应的失调平衡可预测持续性和死亡率。某些抗生素，以及脂磷壁酸（LTA）释放的S。金黄色葡萄球菌可以调节离体免疫反应。在此，我们评估了三种抗葡萄球菌抗生素（万古霉素、替地唑胺和达托霉素）对暴露于高（10 μg）和低（1 μg）剂量LTA的人外周血单核细胞（PBMC）中细胞因子和免疫活化（TNFα、HLA-DR）和免疫麻痹（IL-10、PD-L1）的细胞表面标志物表达的影响。结果表明，LTA与诱导抗炎和促炎免疫应答之间存在剂量依赖性关系。在高LTA条件下显著观察到不同的抗生素效应，但在低LTA条件下不显著。万古霉素显著诱导IL-10和TNFα表达，而达托霉素对细胞因子应答或细胞表面受体表达无影响。替地唑胺增加TNFα和适度增加HLA-DR表达，表明刺激作用。这些研究结果表明，抗葡萄球菌药物差异改变LTA介导的免疫细胞活化状态和细胞因子反应，为未来的临床研究提供支持，以更好地阐明宿主-微生物-抗生素相互作用的复杂性，从而有助于指导精确治疗S。金黄色菌血症
In Staphylococcus aureus bacteremia, our group has shown that a dysregulated balance of pro- and anti-inflammatory cytokine response biased towards an immunoparalysis phenotype is predictive of persistence and mortality, despite receipt of antibiotics. Certain antibiotics, as well as lipoteichoic acid (LTA) released from S. aureus, can modulate immune response ex vivo. Here, we evaluated the effects of three anti-staphylococcal antibiotics (vancomycin, tedizolid, and daptomycin) on the expression of cytokines and cell surface markers of immune activation (TNFα, HLA-DR) and immunoparalysis (IL-10, PD-L1) in human peripheral blood mononuclear cells (PBMC) exposed to high (10 μg) and low (1 μg) doses of LTA. Results suggested a dose-dependent relationship between LTA and induction of anti- and pro-inflammatory immune responses. Differential antibiotic effects were prominently observed at high but not low LTA condition. Vancomycin significantly induced IL-10 and TNFα expression, whereas daptomycin had no effects on cytokine response or expression of cell surface receptors. Tedizolid increased TNFα and modestly increased HLA-DR expression, suggesting a stimulatory effect. These findings suggest that anti-staphylococcal agents differentially alter LTA-mediated immune cell activation status and cytokine response, providing support for future clinical studies to better elucidate the complexities of host–microbial–antibiotic interaction that can help direct precision therapy for S. aureus bacteremia.
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DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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DOI：
10.1186/cc13179
发表时间：
2014-01-06
期刊：
Critical care (London, England)
影响因子：
--
作者：
Monneret G;Venet F
通讯作者：
Venet F
影响因子：
11.8
作者：
Minejima, Emi;Mai, Nikki;Wong-Beringer, Annie
通讯作者：
Wong-Beringer, Annie
影响因子：
4.6
作者：
Wang, Jinhai;Roderiquez, Gregory;Norcross, Michael A.
通讯作者：
Norcross, Michael A.
影响因子：
5.6
作者：
Rockel C;Hartung T
通讯作者：
Hartung T