Gene Center and Department of Biochemistry, Ludwig Maximilians Universität, Munich, Germany.
Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria.
Curr Opin Immunol. 2024 Oct;90:102457. doi: 10.1016/j.coi.2024.102457. Epub 2024 Sep 3.
The innate immune system employs two different strategies to detect pathogens: first, it recognizes microbial components as ligands of pattern recognition receptors (pattern-triggered immunity [PTI]), and second, it detects the activities of pathogen-encoded effectors (effector-triggered immunity [ETI]). Recently, these pathogen-centric concepts were expanded to include sensing of self-derived signals during cellular distress or damage (damage-triggered immunity [DTI]). This extension relied on broadening the PTI model to include damage-associated molecular patterns (DAMPs). However, applying the pattern recognition framework of PTI to DTI overlooks the critical role of sterile activation of ETI pathways. We argue that both PTI and ETI pathways are prone to erroneous detection of self, which is largely attributable to 'friendly fire' rather than protective immune activation. This erroneous activation is inherent to the trade-off between sensitivity and specificity of immune sensing and might be tolerated because its detrimental effects emerge late in life, a phenomenon known as antagonistic pleiotropy.
首先，它将微生物成分识别为模式识别受体的配体（模式触发免疫[PTI]），其次，它检测病原体编码效应物的活性（效应物触发免疫[ETI]）。最近，这些以病原体为中心的概念被扩展到包括在细胞应激或损伤期间检测自身衍生信号（损伤触发免疫[DTI]）。这种扩展依赖于将 PTI 模型扩展到包括损伤相关分子模式（DAMPs）。然而，将 PTI 的模式识别框架应用于 DTI 忽略了 ETI 途径无菌激活的关键作用。我们认为，PTI 和 ETI 途径都容易错误地检测到自身，这主要归因于“友军火力”而不是保护性免疫激活。这种错误的激活是免疫感应的敏感性和特异性之间的权衡所固有的，并且可能被容忍，因为其有害影响出现在生命后期，这种现象称为拮抗多效性。
