Relative roles of complement factor 3 and mannose-binding lectin in host defense against infection
Relative roles of complement factor 3 and mannose-binding lectin in host defense against infection
复制标题
DOI：
10.1128/iai.73.12.8188-8193.2005
复制
发表时间：
2005-12-01
影响因子：
3.1
通讯作者：
Ezekowitz, RAB
中科院分区：
文献类型：
--
作者：
Takahashi, K;Shi, L;Ezekowitz, RAB
金黄色葡萄球菌是严重的医院和社区获得性感染的主要原因。吞噬细胞和体液分子，包括补体，已经被提出在宿主防御革兰氏阳性菌中合作。间接证据表明补体的作用，但这还没有正式定义。补体激活由经典途径、替代途径或凝集素途径启动，后者需要甘露糖结合凝集素（MBL，也称为甘露糖结合蛋白）。MBL是一种寡聚血清蛋白，它识别修饰广泛感染因子（包括沙门氏菌）的碳水化合物。金黄色。我们以前报道过MBL基因敲除小鼠对S.金黄色葡萄球菌感染，证实MBL在一线宿主防御中起关键作用。在这项研究中，我们评估了C3和MBL对S的相对作用。通过产生MBL X C3缺失小鼠以与C3单一缺失小鼠进行比较来观察金黄色葡萄球菌感染。单独的C3缺乏显著地将野生型小鼠的存活率从97%降低到19%（P < 0.0001）。令人惊讶的是，额外的MBL缺乏使存活率进一步降低至7%（P < 0.0001）。然而，单独的MBL缺乏对存活率的影响较小，但显著，为77%（与野生型小鼠相比P = 0.018）。这些结果证实了补体在宿主抗S.金黄色葡萄球菌感染，但也确定了一个MBL依赖的机制，是C3独立的。
Staphylococcus aureus is a major cause of severe nosocomial and community-acquired infections. Phagocytes and humoral molecules, including complement, have been proposed to cooperate in host defense against gram-positive bacteria. Circumstantial evidence indicates a role for complement, but this has not been formally defined. Complement activation is initiated by the classical, alternative, or lectin pathway, with the latter requiring mannose-binding lectin (MBL, also known as mannose-binding protein). MBL is an oligomeric serum protein that recognizes carbohydrates decorating a broad range of infectious agents, including S. aureus. We previously reported that MBL null mice were highly susceptible to S. aureus infection, confirming that MBL plays a key role in first-line host defense. In this study, we evaluated the relative roles of C3 and MBL against S. aureus infection by generating MBL X C3 null mice to compare with C3 single null mice. C3 deficiency alone significantly reduced survival to 19% from 97% of wild-type mice (P < 0.0001). Surprisingly, an additional MBL deficiency reduced the survival further to 7% (P < 0.0001). However, the MBL deficiency alone had a smaller though significant effect on survival, which was 77% (P = 0.018 versus wild-type mice). These results confirm an essential function for complement in host resistance against S. aureus infection but also identify an MBL-dependent mechanism that is C3 independent.