Richard D. Bell, E. Abrefi Cann, Bikash Mishra, Melanie Valencia, Qiong Zhang, Mary Huang, Xu Yang, Alberto Carli, Mathias Bostrom, Lionel B. Ivashkiv
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引用次数: 0
摘要
金黄色葡萄球菌(S. aureus)是骨科假体周围关节感染(PJI)的主要细菌病原体。金黄色葡萄球菌会形成生物膜,生物膜能使细菌免受免疫细胞的感染,并诱导细菌进入耐受抗生素的代谢状态,从而促进持续感染。我们开发了一种体外系统来研究金黄色葡萄球菌生物膜在没有浮游细菌的情况下与原代人类单核细胞的相互作用。与之前的体内数据一致,金黄色葡萄球菌生物膜诱导炎症基因(如 TNF 和 IL1B)及其抗炎反调节因子 IL10 的表达。金黄色葡萄球菌生物膜还能激活PD-1配体和IL-1RA的表达,这些分子有可能抑制T细胞功能或保护性Th17细胞的分化。基因诱导不需要单核细胞与生物膜接触,而是由生物膜包被细菌产生的耐热且大于 3 kD 的可溶性因子介导的。生物膜对抑制基因的激活对 Jak 激酶抑制很敏感。这些结果支持了一种不断发展的模式,即生物膜在调节免疫反应中发挥着积极作用,并表明这种作用是通过产生一种可溶性病原体相关分子模式而实现的,这种分子模式是微生物存活的信号。金黄色葡萄球菌生物膜对 T 细胞抑制基因的诱导为了解 PJI 中抑制 T 细胞免疫的机制提供了启示。
Staphyloccocus aureus biofilm, in absence of planktonic bacteria, produces factors that activate counterbalancing inflammatory and immune-suppressive genes in human monocytes
Staphyloccocus aureus (S. aureus) is a major bacterial pathogen in orthopedic periprosthetic joint infection (PJI). S. aureus forms biofilms that promote persistent infection by shielding bacteria from immune cells and inducing an antibiotic-tolerant metabolic state. We developed an in vitro system to study S. aureus biofilm interactions with primary human monocytes in the absence of planktonic bacteria. In line with previous in vivo data, S. aureus biofilm induced expression of inflammatory genes such as TNF and IL1B, and their anti-inflammatory counter-regulator IL10. S. aureus biofilm also activated expression of PD-1 ligands, and IL-1RA, molecules that have the potential to suppress T cell function or differentiation of protective Th17 cells. Gene induction did not require monocyte:biofilm contact and was mediated by a soluble factor(s) produced by biofilm-encased bacteria that was heat resistant and >3 kD in size. Activation of suppressive genes by biofilm was sensitive to suppression by Jak kinase inhibition. These results support an evolving paradigm that biofilm plays an active role in modulating immune responses, and suggest this occurs via production of a soluble vita-pathogen-associated molecular pattern, a molecule that signals microbial viability. Induction of T cell suppressive genes by S. aureus biofilm provides insights into mechanisms that can suppress T cell immunity in PJI.
期刊介绍:
The Journal of Orthopaedic Research is the forum for the rapid publication of high quality reports of new information on the full spectrum of orthopaedic research, including life sciences, engineering, translational, and clinical studies.