Decreased nematode clearance and anti-phosphorylcholine-specific IgM responses in mannose-binding lectin-deficient mice
Decreased nematode clearance and anti-phosphorylcholine-specific IgM responses in mannose-binding lectin-deficient mice
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DOI：
10.1111/imcb.12219
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Lawrence，Rachel A.
中科院分区：
文献类型：
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作者：
Ahmed，Rubina;Cadman，Emma T.;Lawrence，Rachel A.
马来丝虫是一种引起人类淋巴丝虫病的线虫。此前，我们证明甘露糖结合凝集素(MBL)-A是清除B的必需的。在小鼠中，马来丝虫微丝虫病的存在与寄生虫特异性IgM的最高水平有关。人类常见的MBL基因多态性导致MBL低表达，导致反复的细菌感染。此外，这些低表达的人类MBL基因多态导致淋巴丝虫感染的易感性大大增加。事实上，在30年的时间里，与MBL高表达表型相比，低表达表型的人新丝虫感染的增加要高出10倍。人MBL与小鼠MBL-C非常相似，而不是MBL-A；因此，我们研究了小鼠MBL-C在清除微丝虫方面的作用。单独缺乏MBL-C或同时缺乏MBL-A和MBL-C会导致微丝虫清除延迟，并降低小鼠体内寄生虫特异性IgM。B细胞亚群或MBL缺陷小鼠对T依赖或T非依赖抗原的反应能力几乎没有深刻变化。然而，缺乏MBL-A和/或MBL-C会导致对磷胆碱的IgM降低，磷胆碱是丝虫病和细菌抗原的一种成分，这表明无法对这一部分形成熟练的抗体反应，导致微丝虫病清除不足和总体上对丝虫病的易感性。
Brugia malayiis a nematode that causes human lymphatic filariasis. Previously, we showed that mannose‐binding lectin (MBL)‐A is necessary for clearance ofB. malayimicrofilariae in mice and presence of MBL‐A is linked with maximal levels of parasite‐specific IgM. Common human MBL gene polymorphisms result in low MBL expression and lead to recurring bacterial infections. Furthermore, these low‐expressing human MBL polymorphisms result in greatly increased susceptibility to lymphatic filarial infection. Indeed, gain of new filarial infections over a 30‐year period are 10‐fold higher in people with low, compared to high, MBL‐expression phenotypes. Human MBL closely resembles mouse MBL‐C, rather than MBL‐A; therefore, we examined the role of mouse MBL‐C in clearance of microfilariae. Absence of MBL‐C alone, or both MBL‐A and ‐C, resulted in delayed clearance of microfilariae and reduced parasite‐specific IgM in mice. There were few profound changes in B cell sub‐populations or in the ability of MBL‐deficient mice to respond to T‐dependent or T‐independent antigens. However, absence of MBL‐A and/or MBL‐C resulted in reduced IgM to phosphorylcholine, a constituent of filarial and bacterial antigens, suggesting that inability to form proficient antibody responses to this moiety leads to lack of microfilarial clearance and overall susceptibility to filariasis.