Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA.
Nat Immunol. 2014 May;15(5):415-22. doi: 10.1038/ni.2872.
Inappropriate or chronic detection of self nucleic acids by the innate immune system underlies many human autoimmune diseases. We discuss here an unexpected source of endogenous immunostimulatory nucleic acids: the reverse-transcribed cDNA of endogenous retroelements. The interplay between innate immune sensing and clearance of retroelement cDNA has important implications for the understanding of immune responses to infectious retroviruses such as human immunodeficiency virus (HIV). Furthermore, the detection of cDNA by the innate immune system reveals an evolutionary tradeoff: selection for a vigorous, sensitive response to infectious retroviruses may predispose the inappropriate detection of endogenous retroelements. We propose that this tradeoff has placed unique constraints on the sensitivity of the DNA-activated antiviral response, with implications for the interactions of DNA viruses and retroviruses with their hosts. Finally, we discuss how better understanding of the intersection of retroelement biology and innate immunity can guide the way to novel therapies for specific autoimmune diseases.
先天免疫系统对自身核酸的不适当或慢性检测是许多人类自身免疫性疾病的基础。在这里，我们讨论了内源性免疫刺激性核酸的一个意外来源：内源性逆转录元件的逆转录 cDNA。先天免疫感应与逆转录 cDNA 清除之间的相互作用对理解针对人类免疫缺陷病毒 (HIV) 等传染性逆转录病毒的免疫反应具有重要意义。此外，先天免疫系统对 cDNA 的检测揭示了一种进化上的权衡：选择对传染性逆转录病毒产生强烈、敏感的反应可能会导致对内源性逆转录元件的不适当检测。我们提出，这种权衡对 DNA 激活的抗病毒反应的敏感性施加了独特的限制，这对 DNA 病毒和逆转录病毒与其宿主的相互作用具有重要意义。最后，我们讨论了更好地理解逆转录元件生物学和先天免疫之间的交叉点如何为特定自身免疫性疾病的新型治疗方法提供指导。
