奥地利科学院分子生物技术研究所Josef M. Penninger研究小组报道了蝙蝠类器官在上皮表面显示抗病毒反应。相关论文于2025年5月21日发表于国际顶尖学术期刊《自然—免疫学》杂志上。

课题组开发了呼吸和肠道类器官，再现了高致病性马尔堡病毒（MARV）的天然储存库Rothemettthem aegyptiacthem体内上皮的细胞多样性。与人类相比，蝙蝠类器官和粘膜组织表现出先天免疫效应物的高组成表达，包括I型干扰素-ε (IFNε)和IFN刺激基因（ISGs）。在感染多种人畜共患病毒主题（包括MARV）后，蝙蝠类器官强烈诱导I型和III型IFN反应，从而赋予它们抗病毒保护。III型IFNλ3还表现出与病毒无关的自我扩增，作为ISG增强抗病毒免疫。他们的类器官平台揭示了蝙蝠上皮细胞抗病毒免疫的关键特征，可能为病毒疾病恢复力的治疗策略提供信息。

据悉，蝙蝠可以携带引起大流行的病毒主题而不产生疾病。它们对病毒感染的特殊恢复能力背后的机制在很大程度上尚未解决，这就需要开发生理学相关的和遗传上可处理的研究模型。

附：英文原文

Title: Bat organoids reveal antiviral responses at epithelial surfaces

Author: Kellner, Max J., Monteil, Vanessa M., Zelger, Patrick, Pei, Gang, Jiao, Jie, Onji, Masahiro, Nayak, Komal, Zilbauer, Matthias, Balkema-Buschmann, Anne, Dorhoi, Anca, Mirazimi, Ali, Penninger, Josef M.

Issue&Volume: 2025-05-21

Abstract: Bats can host viruses of pandemic concern without developing disease. The mechanisms underlying their exceptional resilience to viral infections are largely unresolved, necessitating the development of physiologically relevant and genetically tractable research models. Here, we developed respiratory and intestinal organoids that recapitulated the cellular diversity of the in vivo epithelium present in Rousettus aegyptiacus, the natural reservoir for the highly pathogenic Marburg virus (MARV). In contrast to human counterparts, bat organoids and mucosal tissue exhibited elevated constitutive expression of innate immune effectors, including type I interferon-ε (IFNε) and IFN-stimulated genes (ISGs). Upon infection with diverse zoonotic viruses, including MARV, bat organoids strongly induced type I and III IFN responses, which conferred robust antiviral protection. Type III IFNλ3 additionally displayed virus-independent self-amplification, acting as an ISG to enhance antiviral immunity. Our organoid platform reveals key features of bat epithelial antiviral immunity that may inform therapeutic strategies for viral disease resilience.

DOI: 10.1038/s41590-025-02155-1

Source: https://www.nature.com/articles/s41590-025-02155-1