The C-Type Lectin Receptor Mincle Binds to Streptococcus pneumoniae but Plays a Limited Role in the Anti-Pneumococcal Innate Immune Response

The C-Type Lectin Receptor Mincle Binds to Streptococcus pneumoniae but Plays a Limited Role in the Anti-Pneumococcal Innate Immune Response
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DOI:
10.1371/journal.pone.0117022
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发表时间:
2015-02-06
期刊:
影响因子:
3.7
通讯作者:
Opitz, Bastian
Opitz, Bastian
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rabes, Anne;Zimmermann, Stephanie;Opitz, Bastian

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先天免疫系统利用C型凝集素受体(CLRs)来识别病原体和自身抗原上的碳水化合物结构。巨噬细胞诱导的C型凝集素(Mincle)是一种FcR γ-偶联凝集素,可与分枝杆菌索状因子以及某些真菌物种结合。然而,由于在细菌感染中的功能还没有得到彻底的研究,我们的目的是检查它们在肺炎链球菌感染中的功能。使用重组表达的CLR-Fc融合蛋白文库的结合研究表明Mincle与肺炎链球菌特异性、Ca 2+依赖性和表型特异性结合。然而,随后对不同的Mincle表达细胞以及Mincle缺陷小鼠进行的实验显示,该受体在肺炎期间的细菌吞噬、嗜中性粒细胞介导的杀伤、细胞因子产生和抗菌免疫应答中的作用有限。总的来说,我们的研究结果表明,Mincle能够识别肺炎链球菌,但不需要抗肺炎球菌的先天免疫反应。
The innate immune system employs C-type lectin receptors (CLRs) to recognize carbohydrate structures on pathogens and self-antigens. The Macrophage-inducible C-type lectin (Mincle) is a FcR gamma-coupled CLR that was shown to bind to mycobacterial cord factor as well as certain fungal species. However, since CLR functions during bacterial infections have not yet been investigated thoroughly, we aimed to examine their function in Streptococcus pneumonia infection. Binding studies using a library of recombinantly expressed CLR-Fc fusion proteins indicated a specific, Ca2+-dependent, and serotype-specific binding of Mincle to Streptococcus pneumonia. Subsequent experiments with different Mincle-expressing cells as well as Mincle-deficient mice, however, revealed a limited role of this receptor in bacterial phagocytosis, neutrophil-mediated killing, cytokine production, and antibacterial immune response during pneumonia. Collectively, our results indicate that Mincle is able to recognize Streptococcus pneumonia but is not required for the anti-pneumococcal innate immune response.