Phenotypic and Functional Characterization of NK Cells in Human Immune Response against the Dimorphic Fungus Paracoccidioides brasiliensis
Phenotypic and Functional Characterization of NK Cells in Human Immune Response against the Dimorphic Fungus Paracoccidioides brasiliensis
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DOI：
10.4049/jimmunol.1102563
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发表时间：
2012-07-15
影响因子：
4.4
通讯作者：
Mamoni, Ronei L.
中科院分区：
文献类型：
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作者：
Longhi, Larissa N. A.;da Silva, Rosiane M.;Mamoni, Ronei L.
除了它们在对抗病毒感染和肿瘤抗性中的作用外，最近的研究表明NK细胞还参与对抗其他感染性疾病的免疫反应。本研究的目的是表征NK细胞在对巴西副球孢子虫的免疫应答中可能发挥的作用。将来自副球孢子菌病患者和健康个体的纯化NK细胞与巴西假单胞菌酵母细胞或巴西假单胞菌感染的单核细胞一起孵育，加入或不加入重组IL-15。我们发现，从副球孢子菌病患者的NK细胞表现出较低的细胞毒性反应与健康人相比。NK细胞能够直接识别并杀死巴西青霉酵母细胞，并且这种活性似乎是颗粒依赖性的但不依赖于穿孔素，而针对巴西青霉感染的单核细胞的细胞毒性是不依赖于穿孔素的。这些结果表明，NK细胞通过直接破坏酵母细胞或通过识别和杀死感染的细胞积极参与针对巴西疟原虫感染的免疫应答。颗粒溶素是细胞毒性效应的可能介质，因为与健康对照相比，在副球孢子菌病患者中检测到的对酵母细胞的细胞毒性活性降低伴随着CD 56（+）颗粒溶素（+）细胞的频率显著降低。此外，我们表明，NK细胞释放颗粒溶素的培养物后，由巴西青霉刺激，这种分子能够杀死酵母细胞在剂量依赖性的方式。另一个重要的发现是，受刺激的NK细胞能够产生促炎细胞因子（IFN-γ和TNF-α），支持其在感染中的免疫调节作用。免疫学杂志，2012，189：935-945。
Besides their role in fighting viral infection and tumor resistance, recent studies have shown that NK cells also participate in the immune response against other infectious diseases. The aim of this study was to characterize the possible role of NK cells in the immune response against Paracoccidioides brasiliensis. Purified NK cells from paracoccidioidomycosis patients and healthy individuals were incubated with P. brasiliensis yeast cells or P. brasiliensis-infected monocytes, with or without the addition of recombinant IL-15. We found that NK cells from paracoccidioidomycosis patients exhibit a lower cytotoxic response compared with healthy individuals. NK cells are able directly to recognize and kill P. brasiliensis yeast cells, and this activity seems to be granule-dependent but perforin-independent, whereas the cytotoxicity against P. brasiliensis-infected monocytes is perforindependent. These results indicate that NK cells participate actively in the immune response against the P. brasiliensis infection either by directly destroying yeast cells or by recognizing and killing infected cells. Granulysin is the possible mediator of the cytotoxic effect, as the reduced cytotoxic activity against the yeast cells detected in patients with paracoccidioidomycosis is accompanied by a significantly lower frequency of CD56(+)granulysin(+) cells compared with that in healthy controls. Furthermore, we show that NK cells released granulysin in cultures after being stimulated by P. brasiliensis, and this molecule is able to kill the yeast cells in a dose-dependent manner. Another important finding is that stimulated NK cells are able to produce proinflammatory cytokines (IFN-gamma and TNF-alpha) supporting their immunomodulatory role in the infection. The Journal of Immunology, 2012, 189: 935-945.