Development of systemic immune dysregulation in a rat trauma model of biomaterial-associated infection

免疫系统 免疫学 免疫失调 败血症 全身炎症 金黄色葡萄球菌 炎症 细胞因子 医学 生物 遗传学 细菌
作者
Casey E. Vantucci,Hyun Hee Ahn,Travis Fulton,Mara L. Schenker,Pallab Pradhan,Levi B. Wood,Robert E. Guldberg,Krishnendu Roy,Nick J. Willett
出处
期刊:Biomaterials [Elsevier]
卷期号:264: 120405-120405 被引量:28
标识
DOI:10.1016/j.biomaterials.2020.120405
摘要

Orthopedic biomaterial-associated infections remain a major clinical challenge, with Staphylococcus aureus being the most common pathogen. S. aureus biofilm formation enhances immune evasion and antibiotic resistance, resulting in a local, indolent infection that can persist long-term without symptoms before eventual hardware failure, bone non-union, or sepsis. Immune modulation is an emerging strategy to combat host immune evasion by S. aureus. However, most immune modulation strategies are focused on local immune responses at the site of infection, with little emphasis on understanding the infection-induced and orthopedic-related systemic immune responses of the host, and their role in local infection clearance and tissue regeneration. This study utilized a rat bone defect model to investigate how implant-associated infection affects the systemic immune response. Long-term systemic immune dysregulation was observed with a significant systemic decrease in T cells and a concomitant increase in immunosuppressive myeloid-derived suppressor cells (MDSCs) compared to non-infected controls. Further, the control group exhibited a regulated and coordinated systemic cytokine response, which was absent in the infection group. Multivariate analysis revealed high levels of MDSCs to be most correlated with the infection group, while high levels of T cells were most correlated with the control group. Locally, the infection group had attenuated macrophage infiltration and increased levels of MDSCs in the local soft tissue compared to non-infected controls. These data reveal the widespread impacts of an orthopedic infection on both the local and the systemic immune responses, uncovering promising targets for diagnostics and immunotherapies that could optimize treatment strategies and ultimately improve patient outcomes.
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