Division of Microbiology, University, Sakado, Japan.
Infect Immun. 2012 Jun;80(6):2053-60. doi: 10.1128/IAI.06232-11. Epub 2012 Mar 26.
Group B streptococci (GBS; Streptococcus agalactiae) are the most common cause of neonatal sepsis and meningitis. Serotype-specific IgG antibody is known to protect neonates against GBS infections by promoting opsonophagocytosis. The L-ficolin-mediated lectin pathway of the complement is also a potential mechanism for opsonization of GBS, because L-ficolin activates the complement after binding to serotype Ib, III, V, VI, and VIII GBS. In the present study, we investigated how L-ficolin and serotype-specific IgG in cord sera contribute to opsonophagocytic killing of GBS. Neither L-ficolin nor serotype-specific IgG concentrations correlated with C3b deposition on serotype Ib and VI GBS, suggesting L-ficolin- and serotype-specific IgG-independent mechanisms of complement activation. The percentage of serotype VIII GBS killed was high regardless of the concentration of L-ficolin and IgG. In contrast, L-ficolin and serotype-specific IgG can each initiate C3b deposition on serotype III and V GBS and promote phagocytosis by polymorphonuclear leukocytes, but L-ficolin and serotype-specific IgG together promote opsonophagocytic killing to a greater extent than does either alone in vitro. This synergy was observed when serotype III-specific IgG concentrations were between 1 and 6 μg/ml and when serotype V-specific IgG concentrations were between 2 and 5 μg/ml. Concentrations of serotype III-specific IgG in cord blood above 7 μg/ml are considered protective for neonates colonized with GBS, but most neonates with IgG levels of less than 7 μg/ml do not develop GBS infections. The data presented here suggest that L-ficolin enhances opsonophagocytosis of serotype III and V GBS when serotype-specific IgG alone is suboptimal for protection.
B 群链球菌(GBS;无乳链球菌)是导致新生儿败血症和脑膜炎的最常见原因。已知血清型特异性 IgG 抗体通过促进调理吞噬作用来保护新生儿免受 GBS 感染。甘露聚糖结合凝集素(ficolin)介导的补体凝集素途径也是调理 GBS 的潜在机制,因为 ficolin 在结合血清型 Ib、III、V、VI 和 VIII GBS 后激活补体。在本研究中,我们研究了脐带血清中的 ficolin 和血清型特异性 IgG 如何促进 GBS 的调理吞噬杀伤作用。ficolin 和血清型特异性 IgG 浓度均与 Ib 和 VI 型 GBS 上 C3b 的沉积无关,表明 ficolin 和血清型特异性 IgG 独立的补体激活机制。无论 ficolin 和 IgG 的浓度如何,VIII 型 GBS 的杀灭率都很高。相比之下,ficolin 和血清型特异性 IgG 均可在 III 和 V 型 GBS 上引发 C3b 沉积并促进多形核白细胞的吞噬作用,但 ficolin 和血清型特异性 IgG 一起在体外比单独使用时更能促进调理吞噬杀伤作用。当 III 型特异性 IgG 浓度在 1 至 6μg/ml 之间,而 V 型特异性 IgG 浓度在 2 至 5μg/ml 之间时,观察到这种协同作用。脐带血中 III 型特异性 IgG 浓度高于 7μg/ml 被认为对 GBS 定植的新生儿具有保护作用,但大多数 IgG 水平低于 7μg/ml 的新生儿不会发生 GBS 感染。这里提出的数据表明,当单独使用血清型特异性 IgG 不足以提供保护时,ficolin 增强了 III 型和 V 型 GBS 的调理吞噬作用。