Expanding group 1 ILCs sustain early CNS defense against Toxoplasma gondii during impaired adaptive response

Specialized immune interfaces of the central nervous system (CNS), as the choroid plexus and meninges, serve as dynamic gatekeepers coordinating the transition from innate to adaptive immunity during neuroinflammatory responses. While this transition is essential for resolving CNS inflammation, the precise temporal and functional bridging of these phases remains incompletely characterized. To elucidate the role of local innate effectors in maintaining CNS protection we employed the model of Toxoplasma gondii -induced neuroinflammation and applied Fingolimod (FTY720) to pharmacologically modulate the S1P receptor and prevent lymphocyte recirculation and CNS infiltration. Despite resulting in impaired T cell infiltration, CNS parasite control was preserved during the acute phase, coinciding with expansion of group 1 innate lymphoid cells (ILCs), including tissue-resident NK cells and type 1 ILCs (ILC1s). High-dimensional profiling indicated that brain-derived ILC1s acquire distinct, tissue-adapted signatures and sustain robust type 1 cytokine responses ( Ifng , Tnf , Irf8 ) crucial for microglial activation and early antiparasitic defense. Collectively, rapidly adapting innate effectors supported early defense in the infected CNS when adaptive immunity was compromised, providing detailed insight into the context-specific orchestration of CNS protection. These results refine the understanding of the innate–adaptive transition during neuroinflammation and position group 1 ILCs as promising targets for neuroprotective immunomodulation.