Rochford Edward T J, Sabaté Brescó Marina, Zeiter Stephan, Kluge Katharina, Poulsson Alexandra, Ziegler Mario, Richards R Geoff, O'Mahony Liam, Moriarty T Fintan
AO Research Institute Davos, Switzerland.
AO Research Institute Davos, Switzerland; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Bone. 2016 Feb;83:82-92. doi: 10.1016/j.bone.2015.10.014. Epub 2015 Oct 23.
Post-traumatic bone fractures are commonly fixed with implanted devices to restore the anatomical position of bone fragments and aid in the healing process. Bacterial infection in this situation is a challenge for clinicians due to the need for aggressive antibiotic therapy, debridement of infected tissues, and the need to maintain fracture stability. The aim of this study was to monitor immune responses that occur during healing and during Staphylococcus aureus infection, in a clinically relevant murine model of fracture fixation. Skeletally mature C57bl/6 mice received a transverse osteotomy of the femur, which was treated with commercially available titanium fracture fixation plates and screws. In the absence of infection, healing of the fracture was complete within 35days and was characterized by elevated Interleukin (IL)-4 and Interferon-gamma secretion from bone-derived cells and expression of these same genes. In contrast, mice inoculated with S. aureus could not heal the fracture within the observation period and were found to develop typical signs of implant-associated bone infection, including biofilm formation on the implant and osteolysis of surrounding bone. The immune response to infection was characterized by a TH17-led bone response, and a pro-inflammatory cytokine-led Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β) soft tissue response, both of which were ineffectual in clearing implant related bone and soft tissue infections respectively. In this murine model, we characterize the kinetics of pro-inflammatory responses to infection, secondary to bone trauma and surgery. A divergent local immune polarization is evident in the infected versus non-infected animals, with the immune response ultimately unable to clear the S. aureus infection.
创伤后骨折通常采用植入装置进行固定，以恢复骨碎片的解剖位置并促进愈合过程。在这种情况下，细菌感染对临床医生来说是一项挑战，因为需要积极的抗生素治疗、清除感染组织，并且需要维持骨折稳定性。本研究的目的是在一个与临床相关的骨折固定小鼠模型中，监测愈合过程以及金黄色葡萄球菌感染期间发生的免疫反应。骨骼成熟的C57bl/6小鼠接受股骨横向截骨术，并用市售的钛骨折固定板和螺钉进行治疗。在没有感染的情况下，骨折在35天内完全愈合，其特征是骨源性细胞分泌的白细胞介素（IL）-4和干扰素-γ升高，以及这些相同基因的表达。相比之下，接种金黄色葡萄球菌的小鼠在观察期内无法愈合骨折，并且出现了与植入物相关的骨感染的典型体征，包括植入物上形成生物膜以及周围骨的骨溶解。对感染的免疫反应的特征是由TH17主导的骨反应，以及由促炎细胞因子主导的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β软组织反应，这两种反应分别在清除与植入物相关的骨和软组织感染方面均无效。在这个小鼠模型中，我们描述了继发于骨创伤和手术的对感染的促炎反应的动力学。在感染与未感染的动物中，明显存在不同的局部免疫极化，免疫反应最终无法清除金黄色葡萄球菌感染。
