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单核细胞增生李斯特菌可诱导肥大细胞形成细胞外诱捕网。

Listeria monocytogenes induces mast cell extracellular traps.

作者信息

Campillo-Navarro Marcia, Leyva-Paredes Kahiry, Donis-Maturano Luis, González-Jiménez Marco, Paredes-Vivas Yuriria, Cerbulo-Vázquez Arturo, Serafín-López Jeanet, García-Pérez Blanca, Ullrich Stephen E, Flores-Romo Leopoldo, Pérez-Tapia Sonia M, Estrada-Parra Sergio, Estrada-García Iris, Chacón-Salinas Rommel

机构信息

Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, ENCB-IPN, Mexico.

Department of Cell Biology, Cinvestav, Instituto Politécnico Nacional, Mexico.

出版信息

Immunobiology. 2017 Feb;222(2):432-439. doi: 10.1016/j.imbio.2016.08.006. Epub 2016 Aug 6.

Abstract

Mast cells play an essential role in different immunological phenomena including allergy and infectious diseases. Several bacteria induce mast cell activation leading to degranulation and the production of several cytokines and chemokines. However, mast cells also have different microbicidal activities such as phagocytosis and the release of DNA with embedded granular proteins known as Mast Cell Extracellular Traps (MCETs). Although previous reports indicate that extracellular bacteria are able to induce MCETs little is known if intracellular bacteria can induce these structures. In this work, we evaluated MCETs induction by the intracellular bacteria Listeria monocytogenes. We found that mast cells released DNA after stimulation with L. monocytogenes, and this DNA was complexed to histone and tryptase. Before extracellular DNA release, L. monocytogenes induced modifications to the mast cell nuclear envelope and DNA was detected outside the nucleus. L. monocytogenes stimulated mast cells to produce significant amounts of reactive oxygen species (ROS) and blocking NADPH oxidase diminished DNA release by mast cells. Finally, MCETs showed antimicrobial activity against L. monocytogenes that was partially blocked when β-hexosaminidase activity was inhibited. These results show that L. monocytogenes induces mast cells to produce microbicidal MCETs, suggesting a role for mast cells in containing infection beyond the induction of inflammation.

摘要

肥大细胞在包括过敏和传染病在内的不同免疫现象中发挥着重要作用。几种细菌可诱导肥大细胞活化,导致脱颗粒以及多种细胞因子和趋化因子的产生。然而,肥大细胞也具有不同的杀菌活性,如吞噬作用以及释放含有颗粒蛋白的DNA,即肥大细胞胞外诱捕网(MCETs)。尽管先前的报道表明胞外细菌能够诱导MCETs的形成,但对于胞内细菌是否能诱导这些结构却知之甚少。在这项研究中,我们评估了胞内细菌单核细胞增生李斯特菌对MCETs的诱导作用。我们发现,单核细胞增生李斯特菌刺激后肥大细胞释放DNA,并且该DNA与组蛋白和类胰蛋白酶结合。在胞外DNA释放之前,单核细胞增生李斯特菌诱导肥大细胞核膜发生改变,并且在细胞核外检测到了DNA。单核细胞增生李斯特菌刺激肥大细胞产生大量活性氧(ROS),抑制NADPH氧化酶可减少肥大细胞DNA的释放。最后,MCETs对单核细胞增生李斯特菌显示出抗菌活性,当β-己糖胺酶活性受到抑制时,这种抗菌活性会部分受阻。这些结果表明,单核细胞增生李斯特菌可诱导肥大细胞产生杀菌性MCETs,提示肥大细胞在控制感染方面的作用不仅仅是诱导炎症。

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