Ficolin-2 Lectin Complement Pathway Mediates Capsule-Specific Innate Immunity Against Invasive Pneumococcal Disease.
Ficolin-2 Lectin Complement Pathway Mediates Capsule-Specific Innate Immunity Against Invasive Pneumococcal Disease.
复制标题
DOI：
10.3389/fimmu.2022.841062
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
Ganaie F
中科院分区：
文献类型：
--
作者：
Nahm MH;Yu J;Calix JJ;Ganaie F
关于凝集素-微生物配体相互作用引起补体凝集素途径（LP）的保护性反应的报道存在冲突。使用荧光显微镜，我们证明了人凝集素ficolin-2结合肺炎链球菌血清型11 A的荚膜多糖依赖于O-乙酰转移酶基因wcjE。这触发了补体沉积并促进被包裹的肺炎球菌的调理吞噬作用。甚至通过wcjE突变导致纤维胶凝蛋白-2配体表达的部分丧失也消除了细菌杀伤。Ficolin-2不与任何肺炎球菌非荚膜结构相互作用，包括磷壁酸。我们描述了多个11 A克隆衍生物表达不同程度的wcjE依赖性表位共同分离的单一血液标本，可能代表微进化的转变对wcjE缺陷人群在侵袭性肺炎球菌疾病（IPD）。我们发现wcjE损害肺炎球菌侵袭力的流行病学证据，支持LP的纤维胶凝蛋白-2轴提供先天的、针对IPD的细菌型特异性血清学保护。事实上，LP是由几个离散的碳水化合物配体触发强调需要重新评估其影响，在一个glycopolymer特定的方式。
Reports conflict regarding which lectin-microbial ligand interactions elicit a protective response from the lectin pathway (LP) of complement. Using fluorescent microscopy, we demonstrate the human lectin ficolin-2 binds to Streptococcus pneumoniae serotype 11A capsule polysaccharide dependent on the O-acetyltransferase gene wcjE. This triggers complement deposition and promotes opsonophagocytosis of encapsulated pneumococci. Even partial loss of ficolin-2 ligand expression through wcjE mutation abrogated bacterial killing. Ficolin-2 did not interact with any pneumococcal non-capsule structures, including teichoic acid. We describe multiple 11A clonal derivatives expressing varying degrees of wcjE-dependent epitopes co-isolated from single blood specimens, likely representing microevolutionary shifts towards wcjE-deficient populations during invasive pneumococcal disease (IPD). We find epidemiological evidence of wcjE impairing pneumococcal invasiveness, supporting that the LP’s ficolin-2 axis provides innate, serotype-specific serological protection against IPD. The fact that the LP is triggered by only a few discrete carbohydrate ligands emphasizes the need to reevaluate its impact in a glycopolymer-specific manner.
影响因子：
3.7
作者：
Camilli R;Spencer BL;Moschioni M;Pinto V;Berti F;Nahm MH;Pantosti A
通讯作者：
Pantosti A
影响因子：
3.1
作者：
Zhou ML;Frost MR;Xu YC;Nahm MH
通讯作者：
Nahm MH