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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Shielding the double-edged sword: negative regulation of the innate immune system.
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Shielding the double-edged sword: negative regulation of the innate immune system.

机译：屏蔽双刃剑：对先天免疫系统的负面调节。

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摘要

The innate immune system is evolutionarily conserved among all multicellular organisms and is the first line of defense against microorganisms. It enables the host not only to combat pathogenic organisms but also to cohabit with nonpathogenic microorganisms by balancing the host-microorganism interaction. The innate immune response is activated rapidly (within hours) compared with adaptive immunity. Activation of the innate immune system allows the activation of the adaptive immune response by production of proinflammatory cytokines and by providing stimulatory signals via major histocompatibility complex molecules and costimulatory molecules such as CD40, CD80, or CD86; together, these lead to the full activation of both immune systems to fight against pathogenic microorganisms. Activation of the innate immune system, however, can be a double-edged sword for the host. Proinflammatory cytokines mediate a positive feedback loop on the innate immune system, and overproduction of cytokines, if unchecked, is hazardous to the host and may cause severe outcomes such as hyperthermia, organ failure, and even death in extreme cases. Moreover, if the overproduction of proinflammatory cytokines persists, it may cause chronic inflammatory diseases. During evolution, the innate immune system has acquired complicated regulatory systems to control itself so that this "sword" will not kill the host. Various mechanisms including inhibition of Toll-like receptor signaling by interleukin-1 receptor-associated kinase-M have evolved for this purpose and are important not only to fight against pathogenic microorganisms efficiently but also are critical for the peaceful coexistence with commensal bacterial flora.
机译：在所有多细胞生物中，先天免疫系统在进化上是保守的，并且是抵抗微生物的第一道防线。通过平衡宿主与微生物之间的相互作用，它不仅使宿主能够对抗病原生物，而且能够与非致病性微生物同居。与适应性免疫相比，先天免疫反应被迅速激活（数小时内）。先天免疫系统的激活通过促炎细胞因子的产生以及通过主要组织相容性复合分子和共刺激分子（例如CD40，CD80或CD86）提供刺激信号来激活适应性免疫反应。这些共同导致了两个免疫系统的完全激活，以对抗病原微生物。然而，先天免疫系统的激活可能是宿主的一把双刃剑。促炎细胞因子介导先天免疫系统的正反馈回路，如果不加以控制，细胞因子的过度产生对宿主是有害的，并可能导致严重的后果，例如体温过高，器官衰竭甚至在极端情况下甚至死亡。此外，如果持续存在促炎细胞因子的过量生产，则可能引起慢性炎性疾病。在进化过程中，先天免疫系统已经获得了复杂的调节系统来控制自身，因此这把“剑”不会杀死宿主。为此，已经开发出多种机制，包括通过白介素-1受体相关激酶-M抑制Toll样受体信号转导，不仅对有效对抗病原微生物很重要，而且对于与共生细菌菌群的和平共存至关重要。

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