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The murine repeated social defeat (RSD) model reveals that neuroimmune signaling is implicated in the development of stress-induced anxiety-like behavior. Work from our lab showed that the anxiety-like behavior exhibited following RSD is associated with microglial activation, increased recruitment of brain-macrophages, and increased IL-1b expression in the brain. Moreover, this neuroinflammatory process was dependent upon IL-1 receptor 1 in the CNS. To determine the source of cytokine production following stress, NanoString mRNA analysis was conducted on FACS-sorted microglia and brain-macrophages. This revealed that brain macrophages rather than resident microglia are the primary source of increased IL-1b mRNA production in the brain following repeated social defeat. To address the functional role of IL-1b in the development of anxiety-like behavior, caspase-1 knockout (KO) mice were used. Caspase-1 is required for the cleavage of pro-IL-1b into its active form. Results show that caspase-1 KO mice did not develop anxiety-like behavior following RSD. Furthermore, our data indicates that caspase-1 KO mice do not exhibit increased microglial activation as characterized by Iba-1 immunolabeling. However, caspase-1 KO mice still had increased peripheral macrophage trafficking to the brain and increased IL-1b mRNA expression in the brain. We interpret these results to indicate that the development of anxiety-like behavior is dependent on functional IL-1b released by brain macrophages that is cleaved by caspase-1.