Infection Immunology Research Group, Department of Microbial Pathogenesis, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
J Pathol. 2010 Apr;220(5):521-9. doi: 10.1002/path.2664.
Epidemiological studies have shown that the elderly are at higher risk of severe Streptococcus pyogenes infections. In this study, we used a mouse model that displays the age-related loss of resistance to S. pyogenes infection seen in humans to investigate the impaired immune mechanism underlying the age-associated susceptibility to this pathogen. Young (2-3 months old) and aged (>20 months old) BALB/c mice were subcutaneously or intravenously inoculated with S. pyogenes and their capacity to control infection was compared. Aged mice showed faster progression of disease, earlier morbidity, and increased mortality when compared with young animals. Since macrophages are critical for host defence against S. pyogenes, we investigated whether susceptibility of aged mice may be due to an age-associated decline in the functionality of these cells. Our results showed that macrophages from aged mice were as capable as those from young animals to uptake and kill S. pyogenes, but the number of resident tissue macrophages was significantly reduced in the aged host. Treatment of aged mice with macrophage colony-stimulating factor (M-CSF) significantly increased the number of resident macrophages and improved their response to infection. Our results indicate that treatment with M-CSF can restore, at least in part, the mechanisms affected by immunosenescence and enhance the natural resistance of aged mice to infection with S. pyogenes.
流行病学研究表明，老年人感染化脓性链球菌的风险更高。在这项研究中，我们使用了一种在小鼠中显示与人类相似的年龄相关的对化脓性链球菌感染易感性丧失的模型，以研究与这种病原体相关的年龄易感性相关的免疫机制受损的原因。年轻（2-3 个月大）和年老（>20 个月大）BALB/c 小鼠通过皮下或静脉接种化脓性链球菌，并比较它们控制感染的能力。与年轻动物相比，年老小鼠疾病进展更快，发病更早，死亡率更高。由于巨噬细胞对宿主防御化脓性链球菌至关重要，我们研究了年老小鼠的易感性是否可能是由于这些细胞的功能随年龄的增长而下降。我们的结果表明，年老小鼠的巨噬细胞与年轻动物的巨噬细胞一样能够摄取和杀死化脓性链球菌，但在年老宿主中，驻留组织巨噬细胞的数量明显减少。用巨噬细胞集落刺激因子（M-CSF）治疗年老小鼠可显著增加驻留巨噬细胞的数量，并改善其对感染的反应。我们的结果表明，M-CSF 的治疗可以恢复至少部分免疫衰老影响的机制，并增强年老小鼠对化脓性链球菌感染的天然抵抗力。
