1st Department of Orthopedics, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Sci Rep. 2020 Jan 28;10(1):1345. doi: 10.1038/s41598-020-58420-w.
The high incidence of osteomyelitis in vulnerable populations like those with multiple injuries or elderly undergoing joint arthroplasties generates the question what may be their responses to subsequent infection by high virulent isolates. Rabbits were subject to two operations at three week intervals; sham osteomyelitis and sham pyelonephritis (group S); sham osteomyelitis and Escherichia coli pyelonephritis (group P); and Staphylococcus aureus osteomyelitis and E. coli pyelonephritis (group OP). Survival was recorded; cytokine stimulation of circulating mononuclear cells (PBMCs) and tissue myeloperoxidase (MPO) activity and bacterial growth were monitored. In some experiments, dalbavancin treatment was given before pyelonephritis. Healthy PBMCs were pre-treated with bone homogenate, S. aureus or both. Mortality of groups S, P and OP after induction of pyelonephritis was 0%, 50% and 8.3% respectively. Tumour necrosis factor-alpha (TNFα) production by PBMCs was significantly lower in the OP group at 48 hours. E. coli bacterial load was similar in groups P and OP at death or sacrifice whereas the MPO activity of group OP was decreased. Production of TNFα was further decreased among dalbavancin treated rabbits; in these rabbits tissue MPO was increased. TNFα production decreased when healthy PBMCs pre-treated with bone homogenate, S. aureus (HKSA) or both were stimulated with E. coli (HKEC); production was further decreased in the presence of anti-TLR4 and anti-TLR9. It is concluded that staphylococcal osteomyelitis modulated the innate immune responses of the host leading to protection from death by highly virulent E. coli. Tolerance to TLR ligands is the most likely mechanism of action.
高发率的骨髓炎在弱势群体中存在，例如多发伤或老年人群接受关节置换术，这引发了一个问题，即这些人群对后续高毒力分离株感染的反应可能是什么。兔子在三周的间隔内接受了两次手术；假骨髓炎和假肾盂肾炎（S 组）；假骨髓炎和大肠杆菌肾盂肾炎（P 组）；金黄色葡萄球菌骨髓炎和大肠杆菌肾盂肾炎（OP 组）。记录存活率；监测循环单核细胞（PBMC）和组织髓过氧化物酶（MPO）活性的细胞因子刺激和细菌生长。在一些实验中，在肾盂肾炎之前给予达巴万星治疗。健康的 PBMC 用骨匀浆、金黄色葡萄球菌或两者预先处理。诱导肾盂肾炎后，S、P 和 OP 组的死亡率分别为 0%、50%和 8.3%。OP 组 PBMC 在 48 小时时 TNFα 的产生显著降低。死亡或牺牲时，P 和 OP 组的大肠杆菌细菌负荷相似，而 OP 组的 MPO 活性降低。达巴万星治疗的兔子 TNFα 的产生进一步降低；这些兔子的组织 MPO 增加。用骨匀浆、金黄色葡萄球菌（HKSA）或两者预处理的健康 PBMC 刺激大肠杆菌（HKEC）时，TNFα 的产生减少；在存在抗 TLR4 和抗 TLR9 时，产量进一步降低。结论是金黄色葡萄球菌骨髓炎调节了宿主的固有免疫反应，从而使其免受高毒力大肠杆菌的死亡。对 TLR 配体的耐受可能是其作用机制。
