Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2013 Aug 2;8(8):e69739. doi: 10.1371/journal.pone.0069739. Print 2013.
The objectives of this study were to investigate the immune response to intradermal immunization with wall teichoic acid (WTA) and the effect of MBL deficiency in a murine model of infection with methicillin-resistant Staphylococcus aureus (MRSA). WTA is a bacterial cell wall component that is implicated in invasive infection. We tested susceptibility to MRSA infection in wild type (WT) and MBL deficient mice using two strains of MRSA: MW2, a community-associated MRSA (CA-MRSA); and COL, a healthcare-associated MRSA (HA-MRSA). We also performed in vitro assays to investigate the effects of anti-WTA IgG containing murine serum on complement activation and bacterial growth in whole blood. We found that MBL knockout (KO) mice are relatively resistant to a specific MRSA strain, MW2 CA-MRSA, compared to WT mice, while both strains of mice had similar susceptibility to a different strain, COL HA-MRSA. Intradermal immunization with WTA elicited and augmented an anti-WTA IgG response in both WT and MBL KO mice. WTA immunization significantly reduced susceptibility to both MW2 CA-MRSA and COL HA-MRSA, independent of the presence of MBL. The protective mechanisms of anti-WTA IgG are mediated at least in part by complement activation and clearance of bacteria from blood. The significance of these findings is that 1) Intradermal immunization with WTA induces production of anti-WTA IgG; and 2) This anti-WTA IgG response protects from infection with both MW2 CA-MRSA and COL HA-MRSA even in the absence of MBL, the deficiency of which is common in humans.
本研究的目的是研究经皮免疫壁磷壁酸(WTA)后的免疫反应以及 MBL 缺乏对耐甲氧西林金黄色葡萄球菌(MRSA)感染的小鼠模型的影响。WTA 是一种细菌细胞壁成分,与侵袭性感染有关。我们使用两种 MRSA 菌株(MW2,一种社区相关的 MRSA(CA-MRSA);和 COL,一种医疗保健相关的 MRSA(HA-MRSA))在野生型(WT)和 MBL 缺乏的小鼠中测试对 MRSA 感染的易感性。我们还进行了体外实验,以研究含有抗 WTA IgG 的鼠血清对全血中补体激活和细菌生长的影响。我们发现,与 WT 小鼠相比,MBL 敲除(KO)小鼠对特定的 MRSA 菌株 MW2 CA-MRSA 相对具有抗性,而两种菌株的小鼠对不同菌株 COL HA-MRSA 的易感性相似。WTA 皮内免疫在 WT 和 MBL KO 小鼠中均能引发和增强抗 WTA IgG 反应。WTA 免疫接种显著降低了对 MW2 CA-MRSA 和 COL HA-MRSA 的易感性,与 MBL 的存在无关。抗 WTA IgG 的保护机制至少部分通过补体激活和从血液中清除细菌来介导。这些发现的意义在于:1)经皮免疫 WTA 可诱导产生抗 WTA IgG;2)即使在缺乏 MBL 的情况下,这种抗 WTA IgG 反应也能保护免受 MW2 CA-MRSA 和 COL HA-MRSA 的感染,而 MBL 的缺乏在人类中很常见。