Institute for Clinical Chemistry and Clinical Pharmacology, Unit for Clinical Biochemistry, University Hospital, University of Bonn, Bonn, Germany.
Immunol Cell Biol. 2012 May;90(5):474-82. doi: 10.1038/icb.2012.11. Epub 2012 Mar 27.
A successful antimicrobial immune response involves the coordinate action of cells and soluble factors, with the cytokine family of type I interferons (IFNs) having a central role. Type I IFNs are not only crucial in conferring immediate antimicrobial, most importantly antiviral effects, but they also have an essential role in bridging the innate with the adaptive immune response. Therefore, production of these key cytokines must be tightly controlled. To this effect the host has evolved a set of pattern recognition receptors (PRRs) that reliably and specifically detect the presence of microbial pathogens before mounting an IFN response. Most PRR pathways that are known to induce type I IFNs are triggered upon recognition of nucleic acids. This mode of sensing is not straightforward, as large amounts of RNA and DNA are also present within the host. Nevertheless, in some cases distinct molecular features that are present within foreign nucleic acids but absent in endogenous nucleic acids, allow the host to reliably discriminate between 'self' and 'non-self'. At the same time, compartmentalization of PRRs within subcellular organelles that are usually devoid of host nucleic acids, but are sites of pathogen localization, is another principle that enables the host to distinguish self from non-self. The latter mode of sensing applies to the detection of microbial DNA within the cytoplasm, a compartment in which host DNAs are usually not present. Despite the past years' tremendous progress in the field of innate immunity, our understanding of cytoplasmic DNA sensing mechanisms is only beginning to form/take form. In this review, we outline the recent advancements in the elucidation of intracellular DNA-sensing pathways and discuss the future directions of this emerging field.
成功的抗菌免疫反应涉及细胞和可溶性因子的协调作用，I 型干扰素（IFN）细胞因子家族在其中起着核心作用。I 型干扰素不仅在赋予立即的抗菌、最重要的抗病毒作用方面至关重要，而且在连接先天免疫和适应性免疫反应方面也起着重要作用。因此，这些关键细胞因子的产生必须受到严格控制。为此，宿主进化出了一套模式识别受体（PRR），这些受体能够可靠且特异性地检测微生物病原体的存在，然后再引发 IFN 反应。目前已知的大多数诱导 I 型 IFN 的 PRR 途径都是在识别核酸时触发的。这种感应模式并不简单，因为大量的 RNA 和 DNA 也存在于宿主中。然而，在某些情况下，存在于外来核酸中但不存在于内源性核酸中的独特分子特征，使宿主能够可靠地区分“自我”和“非自我”。同时，将 PRR 分隔在通常不含宿主核酸但病原体定位的亚细胞细胞器内，是宿主区分自我和非我的另一个原则。后一种感应模式适用于细胞质中微生物 DNA 的检测，细胞质是宿主 DNA 通常不存在的部位。尽管过去几年在先天免疫领域取得了巨大进展，但我们对细胞质 DNA 感应机制的理解才刚刚开始形成/形成。在这篇综述中，我们概述了阐明细胞内 DNA 感应途径的最新进展，并讨论了这一新兴领域的未来方向。
