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We have previously shown that sustained expression of IL-1\u03b2 in the hippocampus of APP\/PS1 mice decreases amyloid plaque burden independent of recruited CCR2<jats:sup>+<\/jats:sup>myeloid cells, suggesting resident microglia as the main phagocytic effectors of IL-1\u03b2-induced plaque clearance. To date, however, the mechanisms of IL-1\u03b2-induced plaque clearance remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To determine whether microglia are involved in IL-1\u03b2-induced plaque clearance, APP\/PS1 mice induced to express mature human IL-1\u03b2 in the hippocampus via adenoviral transduction were treated with the A\u03b2 fluorescent probe methoxy-X04 (MX04) and microglial internalization of fibrillar A\u03b2 (fA\u03b2) was analyzed by flow cytometry and immunohistochemistry. To assess microglial proliferation, APP\/PS1 mice transduced with IL-1\u03b2 or control were injected intraperitoneally with BrdU and hippocampal tissue was analyzed by flow cytometry. RNAseq analysis was conducted on microglia FACS sorted from the hippocampus of control or IL-1\u03b2-treated APP\/PS1 mice. These microglia were also sorted based on MX04 labeling (MX04<jats:sup>+<\/jats:sup>and MX04<jats:sup>\u2212<\/jats:sup>microglia).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Resident microglia (CD45<jats:sup>lo<\/jats:sup>CD11b<jats:sup>+<\/jats:sup>) constituted &gt; 70% of the MX04<jats:sup>+<\/jats:sup>cells in both Phe- and IL-1\u03b2-treated conditions, and &lt; 15% of MX04<jats:sup>+<\/jats:sup>cells were recruited myeloid cells (CD45<jats:sup>hi<\/jats:sup>CD11b<jats:sup>+<\/jats:sup>). However, IL-1\u03b2 treatment did not augment the percentage of MX04<jats:sup>+<\/jats:sup>microglia nor the quantity of fA\u03b2 internalized by individual microglia. Instead, IL-1\u03b2 increased the total number of MX04<jats:sup>+<\/jats:sup>microglia in the hippocampus due to IL-1\u03b2-induced proliferation. In addition, transcriptomic analyses revealed that IL-1\u03b2 treatment was associated with large-scale changes in the expression of genes related to immune responses, proliferation, and cytokine signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These studies show that IL-1\u03b2 overexpression early in amyloid pathogenesis induces a change in the microglial gene expression profile and an expansion of microglial cells that facilitates A\u03b2 plaque clearance.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-019-1645-7","type":"journal-article","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T09:03:20Z","timestamp":1575968600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["IL-1\u03b2-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia"],"prefix":"10.1186","volume":"16","author":[{"given":"F\u00e1tima","family":"Rivera-Escalera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Pinney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Owlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juilee","family":"Thakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Olschowka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1246-3363","authenticated-orcid":false,"given":"M. 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