Background

Whooping cough is caused by infection of the airways with Bordetella pertussis (Bp). As IFN-γ is essential for protective immunity against Bp we investigated how IFN-γ is induced by Bp or the virulence antigens FHA, Prn or PT, and how IFN-γ contributes to local immune responses in humans.

Methods

PBMCs from healthy donors and/or respiratory epithelial cells were stimulated with soluble antigens or inactivated intact Bp and the presence or absence of blocking antibodies or chemokines. Supernatants and cells were analyzed for IFN-γ and chemokine production and lymphocyte migration tested using epithelial supernatants.

Results

The soluble antigens failed to induce IFN-γ production, whereas inactivated Bp induced IFN-γ production. NK cells were the main source of IFN-γ production, which was enhanced by IL-15. Epithelial–PBMC co-cultures showed robust IFN-γ-dependent CXCL9 and CXCL10 production by the epithelial cells following stimulation with IFN-γ and Bp. The epithelial-derived chemokines resulted in CXCR3-dependent recruitment of NK and T cells.

Conclusions

Inactivated Bp, but not antigens, induced potent IFN-γ production by NK cells, resulting in chemo-attraction of lymphocytes towards the respiratory epithelium. These data provide insight into the requirements for IFN-γ production and how IFN-γ enhances local immune responses to prevent Bp-mediated disease.

中文翻译：

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百日咳博德特氏菌诱导 NK 细胞产生 IFN-γ，导致呼吸道上皮细胞产生化学吸引

背景

百日咳是由百日咳博德特氏菌 (Bp) 感染呼吸道引起的。由于 IFN-γ 对于 Bp 的保护性免疫至关重要，我们研究了 IFN-γ 如何被 Bp 或毒力抗原 FHA、Prn 或 PT 诱导，以及 IFN-γ 如何促进人类的局部免疫反应。

方法

来自健康供体和/或呼吸道上皮细胞的 PBMCs 用可溶性抗原或灭活的完整 Bp 以及阻断抗体或趋化因子的存在或不存在进行刺激。分析上清液和细胞的 IFN-γ 和趋化因子的产生，并使用上皮上清液测试淋巴细胞迁移。

结果

可溶性抗原不能诱导 IFN-γ 的产生，而灭活的 Bp 则诱导 IFN-γ 的产生。NK 细胞是 IFN-γ 产生的主要来源，IL-15 增强了这一点。上皮-PBMC 共培养物显示，在用 IFN-γ 和 Bp 刺激后，上皮细胞产生了强健的 IFN-γ 依赖性 CXCL9 和 CXCL10。上皮来源的趋化因子导致 NK 和 T 细胞的 CXCR3 依赖性募集。

结论

灭活的 Bp，而不是抗原，诱导 NK 细胞产生有效的 IFN-γ，导致淋巴细胞对呼吸道上皮细胞的化学吸引。这些数据深入了解了 IFN-γ 产生的要求以及 IFN-γ 如何增强局部免疫反应以预防 Bp 介导的疾病。