Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides.
Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides.
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DOI：
10.4049/jimmunol.1101703
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Di Nardo A
中科院分区：
文献类型：
--
作者：
Wang Z;Lai Y;Bernard JJ;Macleod DT;Cogen AL;Moss B;Di Nardo A
肥大细胞（MC）是众所周知的过敏反应的效应器，被认为是皮肤和粘膜中的哨兵。此外，通过产生凯萨林菌素，肥大细胞具有抵抗入侵病原体的能力。因此，我们假设肥大细胞可以作为哨兵在皮肤上对病毒感染使用抗菌肽。在这里，我们表明，肥大细胞反应牛痘病毒（VV）和脱乙酰基使用膜激活的途径，导致抗菌肽放电和病毒灭活。这一发现得到了病毒感染小鼠模型的支持。肥大细胞缺陷（Kitwsh−/−）小鼠比野生型动物更容易受到皮肤VV感染，而皮肤中肥大细胞重建的Kitwsh−/−小鼠对VV表现出正常反应。利用来源于缺乏抗菌肽的小鼠的肥大细胞，我们发现抗菌肽是体内皮肤感染中重要的抗病毒颗粒成分。总之，我们的论文表明：MC的存在保护小鼠免受VV皮肤感染。MC脱粒是保护小鼠免受VV所必需的。VV的L1融合进入蛋白的中和抗体通过阻止病毒膜脂质对S1 PR 2的活化而明显抑制脱粒。肥大细胞颗粒释放抗菌肽是抑制VV感染所必需的。
Mast cells (MCs) are well known effectors of allergic reactions and are considered sentinels in the skin and mucosa. In addition, through their production of cathelicidin, mast cells have the capacity to oppose invading pathogens. We therefore hypothesized that mast cells could act as sentinels in the skin against viral infections using antimicrobial peptides. Here, we demonstrate that mast cells react to Vaccinia virus (VV) and degranulate using a membrane-activated pathway that leads to antimicrobial peptide discharge and virus inactivation. This finding was supported using a mouse model of viral infection. Mast cell-deficient (Kitwsh−/−) mice were more susceptible to skin VV infection than the wild-type animals, while Kitwsh−/− mice reconstituted with mast cells in the skin showed a normal response to VV. Using mast cells derived from mice deficient in cathelicidin antimicrobial peptide, we showed that antimicrobial peptides are one important antiviral granule component in vivo skin infections. In conclusion, our paper demonstrates that: MC presence protects mice from VV skin infection. MC degranulation is required for protecting mice from VV. Neutralizing antibody to the L1 fusion entry protein of VV inhibits degranulation apparently by preventing S1PR2 activation by viral membrane lipids. Antimicrobial peptide release from mast cell granules is necessary to inactivate VV infectivity.
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影响因子：
3.7
作者：
Bengali, Zain;Townsley, Alan C.;Moss, Bernard
通讯作者：
Moss, Bernard
影响因子：
3.7
作者：
DALLO, S;RODRIGUEZ, JF;ESTEBAN, M
通讯作者：
ESTEBAN, M
DOI：
10.1038/nri2782
发表时间：
2010-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.7
作者：
Collins, Tony J.
通讯作者：
Collins, Tony J.
影响因子：
3
作者：
Dean, R. E.;O'Brien, L. M.;Ulaeto, D. O.
通讯作者：
Ulaeto, D. O.