Translational Immunology Lab, Institut Pasteur, Université de Paris, Paris, France.
BioPôle Alfort, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
Front Immunol. 2021 Nov 1;12:735866. doi: 10.3389/fimmu.2021.735866. eCollection 2021.
Bats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this symbiotic relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this, we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but were not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.
蝙蝠是唯一具有自主飞行能力的哺乳动物，占所有现存哺乳动物多样性的 20%。此外，它们还携带许多新兴和重现的病毒，包括多种冠状病毒，其中一些在其他哺乳动物中具有高度致病性，但在蝙蝠中不会引起疾病。蝙蝠和病毒之间这种共生关系是如何存在的，目前还不完全清楚。现有证据支持固有免疫系统，特别是 I 型干扰素（IFN）反应，在抗病毒免疫中起主要作用。之前对蝙蝠的研究表明，IFN 途径的成分在转录水平上持续激活。在这项研究中，我们检验了蝙蝠 I 型 IFN 反应也在蛋白质水平上持续激活的假设。为此，我们使用了先前为人类开发的高度敏感的单分子（Simoa）数字 ELISA 检测法，并将其适用于蝙蝠样本。我们前瞻性地从法国动物园采集了四种非本土翼手目物种。我们在健康蝙蝠的循环中发现了 IFNα 蛋白的组成型表达，其浓度在人类中具有生理活性。表达水平因所检查的物种而异，但与年龄、性别或健康状况无关，这表明 IFNα 蛋白的组成型表达独立于疾病。这些结果证实了蝙蝠物种中存在独特的 IFN 反应，这可能解释了它们在没有病理的情况下与多种病毒共存的能力。这些结果可能有助于管理潜在的人畜共患病毒库，并可能确定新的抗病毒策略。
