The oropharyngeal mucosa serves as a perpetual pathogen entry point and a critical site for viral replication and spread. Here, we demonstrate that type 1 innate lymphoid cells (ILC1s) were the major immune force providing early protection during acute oral mucosal viral infection. Using intravital microscopy, we show that ILC1s populated and patrolled the uninfected labial mucosa. ILC1s produced interferon-γ (IFN-γ) in the absence of infection, leading to the upregulation of key antiviral genes, which were downregulated in uninfected animals upon genetic ablation of ILC1s or antibody-based neutralization of IFN-γ. Thus, tonic IFN-γ production generates increased oral mucosal viral resistance even before infection. Our results demonstrate barrier-tissue protection through tissue surveillance in the absence of rearranged-antigen receptors and the induction of an antiviral state during homeostasis. This aspect of ILC1 biology raises the possibility that these cells do not share true functional redundancy with other tissue-resident lymphocytes.

口咽粘膜作为永久病原体进入点和病毒复制和传播的关键部位。在这里，我们证明 1 型先天淋巴细胞 (ILC1s) 是在急性口腔黏膜病毒感染期间提供早期保护的主要免疫力量。使用活体显微镜，我们显示 ILC1 在未感染的唇粘膜中聚集和巡逻。ILC1s 在没有感染的情况下产生干扰素-γ (IFN-γ)，导致关键抗病毒基因的上调，这些基因在 ILC1s 基因消融或基于抗体的 IFN-γ 中和后在未感染动物中下调。因此，即使在感染之前，强效 IFN-γ 的产生也会增加口腔黏膜病毒的抵抗力。我们的研究结果表明，通过在没有重排抗原受体的情况下进行组织监测和在体内平衡期间诱导抗病毒状态来保护屏障组织。ILC1 生物学的这一方面提出了这些细胞不与其他组织驻留淋巴细胞共享真正功能冗余的可能性。