Institute of Inflammation and Neurodegeneration, Health Campus Immunology, Infectiology, and Inflammation (GC-I(3)), Otto von Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany.
Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology, and Inflammation (GC-I(3)), Otto-von-Guericke University, Magdeburg, Germany.
Cell Rep. 2022 Mar 29;38(13):110564. doi: 10.1016/j.celrep.2022.110564.
Cerebral infections are restrained by a complex interplay of tissue-resident and recruited peripheral immune cells. Whether innate lymphoid cells (ILCs) are involved in the orchestration of the neuroinflammatory dynamics is not fully understood. Here, we demonstrate that ILCs accumulate in the cerebral parenchyma, the choroid plexus, and the meninges in the onset of cerebral Toxoplasma gondii infection. Antibody-mediated depletion of conventional natural killer (cNK) cells and ILC1s in the early stage of infection results in diminished cytokine and chemokine expression and increased cerebral parasite burden. Using cNK- and ILC1-deficient murine models, we demonstrate that exclusively the lack of ILC1s affects cerebral immune responses. In summary, our results provide evidence that ILC1s are an early source of IFN-γ and TNF in response to cerebral T. gondii infection, thereby inducing host defense factors and initiating the development of a neuroinflammatory response.
脑部感染受到组织驻留和募集的外周免疫细胞的复杂相互作用的限制。先天淋巴细胞（ILCs）是否参与神经炎症动力学的协调尚不完全清楚。在这里，我们证明在大脑弓浆虫感染的开始时，ILCs 会在大脑实质、脉络丛和脑膜中积累。在感染的早期阶段，通过抗体耗竭常规自然杀伤（cNK）细胞和 ILC1 会导致细胞因子和趋化因子表达减少，脑部寄生虫负担增加。使用 cNK 和 ILC1 缺陷型小鼠模型，我们证明仅缺乏 ILC1 会影响大脑免疫反应。总之，我们的研究结果提供了证据表明，ILC1s 是针对大脑弓浆虫感染时 IFN-γ 和 TNF 的早期来源，从而诱导宿主防御因子并启动神经炎症反应的发展。
