Type 1 innate lymphoid cells regulate the onset of Toxoplasma gondii-induced neuroinflammation

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. [Display omitted] •ILCs are present in distinct CNS compartments•cNK cells and ILC1s accumulate during the onset of cerebral toxoplasmosis•ILC1 loss results in reduced IFN-γ levels and increased parasite burden in the brain Steffen et al. report that ILC1s are an early source of IFN-γ in the CNS during the onset of cerebral T. gondii infection. Loss of ILC1s delays the production of IFN-γ-associated host defense factors and subsequent pathogen control.