近日，德国亥姆霍兹感染研究中心（HZI）的科学家研究发现了肥大细胞免疫反应机理，其能使人们对信号物质、免疫细胞和疾病防御这些复杂网络的理解向前迈进一步。相关研究结果发表在近期《美国国家科学院院刊》上。
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在感染的情况下，人体的免疫系统会释放不同的信号物质。这些分子激活免疫细胞，与入侵的病原体做斗争或抑制免疫细胞，以避免过度的炎症反应。因此，免疫系统必须很快决定出什么样的激活和抑制信号物质混合可以带来成功的防御。
现在，位于德国布伦瑞克的亥姆霍兹感染研究中心的研究人员证明，一直以来被低估的免疫细胞，即所谓的肥大细胞，在感染后的几个小时内就已经确定了该如何防御。
肥大细胞在过敏性反应中起核心作用，以前的研究都集中在这个功能上。已知肥大细胞位于皮肤和粘膜下，当过敏原进入人体时立即反应，其结果是粘膜变红，肿胀，流泪和流鼻涕。但现在，研究人员发现，肥大细胞似乎也对防御病原体也起着至关重要的、迄今仍鲜为人知的作用，它们等候在病菌入侵的地方，属于免疫系统防御的第一线。
为了研究肥大细胞如何与细菌接触或应对病毒，HZI的研究人员将肥大细胞和病原体一起放入培养皿中，随后观察肥大细胞产生了哪些信号物质。通常一旦感染了病毒，细胞会形成β-干扰素，但研究人员却探测不到细菌感染的信号物质。因此研究人员认为，这些细胞只在病毒入侵时会形成信号物质β-干扰素，而在细菌感染时却不会。原因是这种分子在帮助抵御病毒的同时会抑制其他重要的杀菌防御细胞，从而损害防御功能。
帮助做出这个决定的是肥大细胞表面的受体：即所谓的Toll样受体（TLR），当有病原体侵入人体时它能激活免疫细胞。当该受体被激活，肥大细胞产生一系列信号物质，用于吸引、阻止、激活或抑制其他细胞，从而调节最佳的免疫反应。
研究人员解释说，要启动β-干扰素反应，免疫细胞必须运输这些受体到细胞内部。但是肥大细胞在细菌感染时不这样做，所以不会产生β-干扰素。因此这表明，肥大细胞能很早“明确”免疫系统行动的方向。(生物谷Bioon.net)
生物谷推荐原文出处：
PNAS doi: 10.1073/pnas.0912551107
Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria
Nicole Dietricha, Manfred Rohdeb, Robert Geffersc, Andrea Kr?gerd, Hansj?rg Hauserd, Siegfried Weissa, and Nelson O. Gekaraa,1,2
Departments of aMolecular Immunology,
bMicrobial Pathogenesis,
cCell Biology, and
dGene Regulation and Differentiation, Helmholtz-Centre for Infection Research, 38124 Braunschweig, Germany
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-β. 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.
