JCI Insight. 2018 May 3;3(9):97339. doi: 10.1172/jci.insight.97339.
Using a mouse retroviral model, we have shown that mAb-based immunotherapy can induce life-long endogenous protective immunity (vaccine-like effects). This observation has potentially important consequences for treating life-threatening human viral infections. Here, we investigated the role of neutrophils in this effect. Neutrophils are innate immunity effector cells with well-established microbe-killing activities that are rapidly mobilized upon infection. They are also emerging as orchestrators of innate and adaptive immunities. However, their immunomodulatory activity during antiviral mAb immunotherapies has never been studied. Our data reveal that neutrophils have an essential role in immunotherapy-induced immune protection of infected mice. Unexpectedly, neutrophils have a limited effect in controlling viral propagation upon passive immunotherapy administration, which is mostly mediated by NK cells. Instead, neutrophils operate as essential inducers of a potent host humoral antiviral response. Thus, neutrophils play an unexpected key role in protective immunity induction by antiviral mAbs. Our work opens approaches to improve antiviral immunotherapies, as it suggests that preserving neutrophil functions and counts might be required for achieving mAb-induced protective immunity.
利用小鼠逆转录病毒模型，我们已经表明，基于单克隆抗体的免疫疗法可以诱导终身内源性保护免疫（类似于疫苗的效果）。这一观察结果对于治疗危及生命的人类病毒感染具有潜在的重要意义。在这里，我们研究了中性粒细胞在这一效应中的作用。中性粒细胞是先天免疫效应细胞，具有成熟的杀菌活性，在感染时会迅速动员。它们也正在成为先天免疫和适应性免疫的协调者。然而，它们在抗病毒单克隆抗体免疫治疗中的免疫调节活性从未被研究过。我们的数据表明，中性粒细胞在感染小鼠的抗病毒治疗诱导免疫保护中起着至关重要的作用。出乎意料的是，中性粒细胞在被动免疫治疗中对控制病毒复制的作用有限，这主要是由自然杀伤细胞介导的。相反，中性粒细胞是诱导宿主体液抗病毒反应的有力诱导剂。因此，中性粒细胞在抗病毒单克隆抗体诱导的保护性免疫中起着意想不到的关键作用。我们的工作为改进抗病毒免疫疗法开辟了途径，因为它表明，为了实现单克隆抗体诱导的保护性免疫，可能需要保留中性粒细胞的功能和计数。
