Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria
Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria
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DOI：
10.1073/pnas.0912551107
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发表时间：
2010-05-11
影响因子：
11.1
通讯作者：
Gekara, Nelson O.
中科院分区：
文献类型：
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作者：
Dietrich, Nicole;Rohde, Manfred;Gekara, Nelson O.
在toll样受体（TLRs）激活后，促炎和I型IFN反应的平衡诱导决定了微生物感染的结果以及自身免疫性和其他炎症性疾病的发病机制。肥大细胞是先天免疫系统的关键组成部分，在过敏和自身免疫中起着削弱作用。然而，它们在抗微生物宿主防御中的作用越来越得到承认。肥大细胞如何与微生物相互作用以及由此引发的反应的性质尚未得到很好的表征。本研究表明，在响应革兰氏阳性和阴性细菌或其成分激活TLR时，肥大细胞会引起促炎反应，但不会引起I型IFN反应。我们证明，在肥大细胞中，结合的细菌和TLR配体仍然被困在细胞表面，不进行内化，这是I型IFN诱导的先决条件。然而，当水泡性口炎病毒进入胞质维甲酸诱导基因I受体时，这些细胞可以引发I型ifn。尽管对抗病毒免疫很重要，但已知强烈的I - IFN反应有助于几种细菌病原体的发病机制，如单核细胞增生李斯特菌。有趣的是，我们观察到肥大细胞依赖的中性粒细胞动员在单核增生乳杆菌感染时受到ifn - β的严重损害。因此，尽管肥大细胞在应对病毒感染时被赋予了引发I型ifn的能力，但在细菌感染时只引发促炎反应，这一事实表明肥大细胞作为先天免疫系统的关键效应细胞，能够很好地调节最佳的抗菌和抗病毒反应。
Balanced induction of proinflammatory and type I IFN responses upon activation of Toll-like receptors (TLRs) determines the outcome of microbial infections and the pathogenesis of autoimmune and other inflammatory diseases. Mast cells, key components of the innate immune system, are known for their debilitating role in allergy and autoimmunity. However, their role in antimicrobial host defenses is being acknowledged increasingly. How mast cells interact with microbes and the nature of responses triggered thereby is not well characterized. Here we show that in response to TLR activation by Gram-positive and -negative bacteria or their components, mast cells elicit proinflammatory but not type I IFN responses. We demonstrate that in mast cells, bound bacteria and TLR ligands remain trapped at the cell surface and do not undergo internalization, a prerequisite for type I IFN induction. Such cells, however, can elicit type I IFNs in response to vesicular stomatitis virus which accesses the cytosolic retinoic acid-inducible gene I receptor. Although important for antiviral immunity, a strong I IFN response is known to contribute to pathogenesis of several bacterial pathogens such as Listeria monocytogenes. Interestingly, we observed that the mast cell-dependent neutrophil mobilization upon L. monocytogenes infection is highly impaired by IFN-beta. Thus, the fact that mast cells, although endowed with the capacity to elicit type I IFNs in response to viral infection, elicit only proinflammatory responses upon bacterial infection shows that mast cells, key effector cells of the innate immune system, are well adjusted for optimal antibacterial and antiviral responses.