Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.

微生物或内源性分子模式以及病原体功能特征可以激活先天免疫系统。尽管已经对模式识别受体对感染的检测进行了详细研究，但对毒力因子活性的检测仍然缺乏表征。在果蝇中，遗传证据表明，丝氨酸蛋白酶Persephone属于由异常蛋白水解活性激活以诱导Toll信号转导的危险途径。但是，尚未确定该途径的激活机制或其特异性。在这里，我们确定了Persephone前域中的一个独特区域，该区域起着外源蛋白酶诱饵的作用，而与它们的起源，类型或特异性无关。在该诱饵区域的切割构成了顺序激活的第一步，并允许随后的Persephone成熟为内源性半胱氨酸组织蛋白酶26-29-p。我们的研究结果将Persephone本身确立为一种免疫受体，能够通过毒力因子的活动而不是分子模式来感知广泛的微生物。