Mice Deficient in Ficolin, a Lectin Complement Pathway Recognition Molecule, Are Susceptible to Streptococcus pneumoniae Infection
Mice Deficient in Ficolin, a Lectin Complement Pathway Recognition Molecule, Are Susceptible to Streptococcus pneumoniae Infection
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DOI：
10.4049/jimmunol.1200836
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发表时间：
2012-12-15
影响因子：
4.4
通讯作者：
Fujita, Teizo
中科院分区：
文献类型：
--
作者：
Endo, Yuichi;Takahashi, Minoru;Fujita, Teizo
甘露糖结合凝集素 (MBL) 和 ficolin 与 MBL 相关丝氨酸蛋白酶（通过凝集素途径激活补体的关键酶）复合，并在先天免疫系统中充当可溶性模式识别分子。尽管大量报道揭示了 MBL 在传染病和自身免疫性疾病中的重要性，但 ficolin 的作用仍不清楚。为了确定 ficolin 在体内的具体作用，我们制作了缺乏 ficolin 的模型小鼠。 ficolin A (FcnA) 缺陷型 (Fcna(-/-)) 和 FcnA/ficolin B 双缺陷型 (Fcna(-/-)b(-/-)) 小鼠血清中缺乏 FcnA 介导的补体激活，因为不存在包含 FcnA 和 MBL 相关丝氨酸蛋白酶的复合物。当通过经鼻感染肺炎链球菌菌株（可被纤维胶蛋白识别但不被 MBL 识别）来评估宿主防御时，与野生型小鼠相比，所有三种纤维胶蛋白缺陷小鼠（Fcna(-/-)、Fcnb(-/-) 和 Fcna(-/-)b(-/-)）的存活率均显着降低。体内 FcnA 介导的凝集素途径的重建提高了 Fcna(-/-) 小鼠的存活率，但没有提高 Fcna(-/-)b(-/-) 小鼠的存活率，这表明 FcnA 和 ficolin B 对于防御肺炎链球菌至关重要。这些结果表明，丝胶蛋白通过凝集素补体途径在针对肺炎球菌感染的先天免疫中发挥着至关重要的作用。免疫学杂志，2012，189：5860-5866。
Mannose-binding lectin (MBL) and ficolin are complexed with MBL-associated serine proteases, key enzymes of complement activation via the lectin pathway, and act as soluble pattern recognition molecules in the innate immune system. Although numerous reports have revealed the importance of MBL in infectious diseases and autoimmune disorders, the role of ficolin is still unclear. To define the specific role of ficolin in vivo, we generated model mice deficient in ficolins. The ficolin A (FcnA)-deficient (Fcna(-/-)) and FcnA/ficolin B double-deficient (Fcna(-/-)b(-/-)) mice lacked FcnA-mediated complement activation in the sera, because of the absence of complexes comprising FcnA and MBL-associated serine proteases. When the host defense was evaluated by transnasal infection with a Streptococcus pneumoniae strain, which was recognized by ficolins, but not by MBLs, the survival rate was significantly reduced in all three ficolin-deficient (Fcna(-/-), Fcnb(-/-), and Fcna(-/-)b(-/-)) mice compared with wild-type mice. Reconstitution of the FcnA-mediated lectin pathway in vivo improved survival rate in Fcna(-/-) but not in Fcna(-/-)b(-/-) mice, suggesting that both FcnA and ficolin B are essential in defense against S. pneumoniae. These results suggest that ficolins play a crucial role in innate immunity against pneumococcal infection through the lectin complement pathway. The Journal of Immunology, 2012, 189: 5860-5866.