Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis
Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis
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DOI：
10.1073/pnas.1611776114
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发表时间：
2017-05-09
影响因子：
11.1
通讯作者：
Javid, Babak
中科院分区：
文献类型：
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作者：
Li, Hao;Wang, Xing-xing;Javid, Babak
Igs 在针对结核病病原体结核分枝杆菌 (Mtb) 感染的自然保护中的作用存在争议。尽管针对分枝杆菌抗原产生的单克隆抗体的被动免疫在小鼠感染模型中显示出保护功效，但在 B 细胞耗尽的动物中的研究仅显示出适度的表型。我们不知道人类是否会产生保护性抗体反应。在这里，我们调查了北京一家结核病医院的医护人员虽然接触了超感染剂量的致病性结核分枝杆菌，但仍然保持健康，是否产生了有效预防结核分枝杆菌感染的抗体反应。我们测试了从 48 名医护人员身上分离出的抗体，并将其与 12 名活动性结核病患者进行了比较。我们发现，在气溶胶小鼠攻击模型中，48 名医护人员中有 7 名的抗体显示出针对 Mtb 的中等保护作用，但活动性结核病患者中没有一人的抗体表现出中等程度的保护作用。有趣的是，七名做出保护性抗体反应的医护人员中，有三人没有证据表明先前曾被干扰素-感染过结核病。释放测定。体内观察到的保护作用与体外人全血测定中 Mtb 的中和作用之间也存在良好的相关性。介导保护作用的抗体针对 Mtb 表面，并依赖于免疫复合物和 CD4+ T 细胞的功效。我们的研究结果表明，某些个体会产生针对结核分枝杆菌的保护性抗体，并对结核病有效免疫反应的本质提出挑战。
The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-. release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.