LL37:DNA复合物对人类巨噬细胞内的细菌具有抗菌活性。
LL37:DNA complexes provide antimicrobial activity against intracellular bacteria in human macrophages.
作者信息
Stephan Alexander, Batinica Marina, Steiger Julia, Hartmann Pia, Zaucke Frank, Bloch Wilhelm, Fabri Mario
机构信息
Department of Dermatology, University of Cologne, Cologne, Germany.
1st Department of Internal Medicine, University of Cologne, Cologne, Germany.
出版信息
Immunology. 2016 Aug;148(4):420-32. doi: 10.1111/imm.12620.
Abstract
As part of the innate host response neutrophils release neutrophil extracellular traps (NETs), protein:DNA complexes that contain a number of antimicrobial peptides (AMPs), such as cathelicidin. Human cathelicidin in its active form, LL37, has potent antimicrobial activity against bacteria. However, whether LL37 derived from NETs contributes to antimicrobial activity against intracellular pathogens remains unclear. Here, we report that NETs induced by mycobacteria contain cathelicidin. Human macrophages internalized NET-bound cathelicidin, which is transported to lysosomal compartments. Furthermore, using a model of in vitro-generated LL37:DNA complexes we found that LL37 derived from such complexes attacks mycobacteria in macrophage phagolysosomes resulting in antimicrobial activity. Taken together, our results suggest a mechanism by which LL37 in complex with DNA contributes to host defence against intracellular bacteria in human macrophages.
摘要
作为先天性宿主反应的一部分，中性粒细胞会释放中性粒细胞胞外诱捕网（NETs），即包含多种抗菌肽（AMPs）（如cathelicidin）的蛋白质：DNA复合物。人源活性形式的cathelicidin即LL37，对细菌具有强大的抗菌活性。然而，源自NETs的LL37是否有助于对抗细胞内病原体的抗菌活性仍不清楚。在此，我们报告分枝杆菌诱导产生的NETs含有cathelicidin。人巨噬细胞内化了与NET结合的cathelicidin，后者被转运至溶酶体区室。此外，利用体外生成的LL37：DNA复合物模型，我们发现源自此类复合物的LL37会攻击巨噬细胞吞噬溶酶体中的分枝杆菌，从而产生抗菌活性。综上所述，我们的结果提示了一种机制，即与DNA结合的LL37有助于人类巨噬细胞抵御细胞内细菌的宿主防御。
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