N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is a neurological disorder mediated by autoantibodies targeting the NMDAR. Patients’ autoantibodies are pathogenic, as they cause neuronal dysfunction in vitro, and molecular and behavioral changes in mouse models of cerebroventricular transfer of patients’ antibodies. Active immunization models have confirmed these effects and informed on the development of adaptive immune responses. Here we aimed to characterize the accompanying innate immune response and how this contributes to disease pathogenesis. Female C57BL/6 mice were immunized with NMDAR or saline, along with AddaVax adjuvant and pertussis toxin. Fourteen days after immunization, blood samples, brain and spleen tissue were collected. NMDAR antibodies were detected by cell-based assays. Brain immune infiltrates (neutrophils, monocytes, macrophages, Natural Killer [NK] and microglial cells) and complement deposition were quantified by confocal imaging. Immune cells were also extracted from brain and spleen tissues, and phenotyped by flow cytometry. NMDAR antibodies were detected in the serum of immunized mice, but not in controls (Fig1A). Brain confocal microscopy showed that, compared to controls, immunized mice had increased complement deposition (Fig1B) and infiltrates of neutrophils, macrophages and NK cells (Fig1C)(immunophenotyping of brain inflammatory infiltrates will be presented). By contrast, flow cytometry of spleen-derived cells revealed a decreased number of NK cells in immunized mice, suggesting a brain-sequestration of some specific immune cells from the periphery. This model of active immunization demonstrates the production of NMDAR antibodies as observed in patients, and suggests the involvement of innate immune responses in the brain during the acute stage of the disease.