Granzyme A (GzmA) is secreted by cytotoxic lymphocytes and has traditionally been viewed as a mediator of cell death. However, a growing body of data suggests the physiological role of GzmA is promotion of inflammation. Here, we show that GzmA is significantly elevated in the sera of chikungunya virus (CHIKV) patients and that GzmA levels correlated with viral loads and disease scores in these patients. Serum GzmA levels were also elevated in CHIKV mouse models, with NK cells the likely source. Infection of mice deficient in type I interferon responses with CHIKV, Zika virus, or dengue virus resulted in high levels of circulating GzmA. We also show that subcutaneous injection of enzymically active recombinant mouse GzmA was able to mediate inflammation, both locally at the injection site as well as at a distant site. Protease activated receptors (PARs) may represent targets for GzmA, and we show that treatment with PAR antagonist ameliorated GzmA- and CHIKV-mediated inflammation.

中文翻译：

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基孔肯雅热和其他虫媒感染中的颗粒酶A。

颗粒酶A（GzmA）由细胞毒性淋巴细胞分泌，传统上被视为细胞死亡的媒介。但是，越来越多的数据表明，GzmA的生理作用是促进炎症。在这里，我们显示在基孔肯雅病毒（CHIKV）患者的血清中GzmA显着升高，并且这些患者中GzmA水平与病毒载量和疾病评分相关。在CHIKV小鼠模型中，血清GzmA水平也升高，而NK细胞可能是来源。用CHIKV，寨卡病毒或登革热病毒感染I型干扰素应答不足的小鼠会导致高水平的循环GzmA。我们还表明，皮下注射的酶活性重组小鼠GzmA能够介导炎症，无论是在注射部位还是在远处。