Granzyme B Produced by Natural Killer Cells Enhances Inflammatory Response and Contributes to the Immunopathology of Cutaneous Leishmaniasis
Granzyme B Produced by Natural Killer Cells Enhances Inflammatory Response and Contributes to the Immunopathology of Cutaneous Leishmaniasis
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DOI：
10.1093/infdis/jiz538
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发表时间：
2020-03-15
影响因子：
6.4
通讯作者：
Carvalho, Lucas P.
中科院分区：
文献类型：
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作者：
Campos, Tais M.;Novais, Fernanda O.;Carvalho, Lucas P.
背景资料。感染巴西利什曼原虫的患者的皮肤损害与细胞毒性CD8(+)T细胞诱导的炎症有关。此外，CD8(+)T细胞介导的细胞毒作用与杀灭寄生虫无关。同时，自然杀伤细胞(NK细胞)在皮肤利什曼病(CL)中所起的细胞毒作用尚不清楚。在本研究中，我们观察到CL患者外周血中NK细胞的频率高于正常人，并且NK细胞比CD8(+)T细胞表达更多的干扰素-γ、肿瘤坏死因子(TNF)、颗粒酶B和穿孔素。我们还发现，CL病变的大部分细胞毒活性是由NK细胞触发的，CL病变产生的高水平颗粒酶B与较大的病变大小有关。此外，体外阻断颗粒酶B可减少肿瘤坏死因子的产生。综上所述，我们的数据提示，NK细胞在诱导CL炎症中起着重要作用，从而有助于疾病免疫病理学。
Background. Skin lesions from patients infected with Leishmania braziliensis has been associated with inflammation induced by cytotoxic CD8(+) T cells. In addition, CD8(+) T cell-mediated cytotoxicity has not been linked to parasite killing. Meanwhile, the cytotoxic role played by natural killer (NK) cells in cutaneous leishmaniasis (CL) remains poorly understood.Methods. In this study, we observed higher frequencies of NK cells in the peripheral blood of CL patients compared with healthy subjects, and that NK cells expressed more interferon-gamma, tumor necrosis factor (TNF), granzyme B, and perforin than CD8(+) T cells.Results. We also found that most of the cytotoxic activity in CL lesions was triggered by NK cells, and that the high levels of granzyme B produced in CL lesions was associated with larger lesion size. Furthermore, an in vitro blockade of granzyme B was observed to decrease TNF production.Concclusions. Our data, taken together, suggest an important role by NK cells in inducing inflammation in CL, thereby contributing to disease immunopathology.