Type 1 Innate Lymphoid Cells Regulate the Early Stage of Toxoplasma Gondii-Induced Neuroinflammation

Abstract

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 initiation of an orchestrated neuroinflammatory response is not fully understood. Here we demonstrate that ILCs accumulate in the cerebral parenchyma, the choroid plexus, and the meninges in the early stage of cerebralToxoplasma gondii infection. Longitudinal analyses revealed that NKp46+NK1.1+Eomes-CD49a+ ILC1-like cells surpass NKp46+NK1.1+Eomes+CD49a- conventional natural killer (cNK) cells in the course of infection. Antibody-mediated depletion of cNK and ILC1s cells resulted in diminished cytokine expression and increased cerebral parasite burden. Using cNK- and ILC1-deficient mouse models, we demonstrate that only the lack of ILC1s affected cerebral immune responses. In summary, our results provide evidence that ILC1-like cells are an early source of IFN‑γ and TNF in response to cerebral T. gondii infection, thereby inducing host defence factors as well as the recruitment of protective Ly6Chi inflammatory monocytes.