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Our group has previously reported that repeated intraperitoneal administration of alum in mice, known as adjuvant conditioning (AC), creates an immunosuppressive environment that delays allogeneic graft rejection through NLRP3-dependent MDSC expansion. However, little is known about the effects of AC on the reprogramming of peritoneal cavity cells, particularly the different peritoneal macrophage populations, and the impact on the adaptive immune response. We found a population-specific immune response to alum, with small peritoneal macrophages (SPMs) being more prone to inflammasome activation than large peritoneal macrophages (LPMs) in vitro. In vivo, alum exposure led to NLRP3-dependent macrophage disappearance reaction (MDR) of LPMs, which could be explained by aggregate formation and migration to the omentum. AC also induced the reprogramming of resident macrophages and infiltrating monocytes towards a less inflammatory state, making them more vulnerable to bacterial infections, but recruited neutrophils with enhanced killing ability. This suggests that AC may influence both innate and adaptive immunity in distinct ways, reprogramming cells to different profiles, and indicating its potential as an immunosuppressive treatment for autoimmune diseases and transplant rejection.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf206","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T23:53:56Z","timestamp":1756857236000},"page":"3604-3617","source":"Crossref","is-referenced-by-count":2,"title":["Adjuvant conditioning enhances neutrophil function while inducing a suppressive peritoneal macrophage phenotype"],"prefix":"10.1093","volume":"214","author":[{"given":"Thais","family":"Boccia","sequence":"first","affiliation":[{"name":"Department of Surgery, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Fattori","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Deroco","family":"Veloso Da Silva","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]},{"name":"Laboratory of Pain, Inflammation, Neuropathy and Cancer, Department of Immunology, Parasitology and General Pathology, Londrina State University , Londrina, PR,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan L","family":"Asquith","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Rogers","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Zanoni","sequence":"additional","affiliation":[{"name":"Division of Immunology, Division of Gastroenterology, Department of Pediatrics, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-7035","authenticated-orcid":false,"given":"Alex G","family":"Cuenca","sequence":"additional","affiliation":[{"name":"Department of Surgery, Boston Children\u2019s Hospital\u2014Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"2025122315374453200_vkaf206-B1","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1097\/TP.0000000000001379","article-title":"Impact of immune-modulatory drugs on Treg","volume":"100","author":"Furukawa","year":"2016","journal-title":"Transplantation"},{"key":"2025122315374453200_vkaf206-B2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1177\/1753425918820427","article-title":"Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin","volume":"25","author":"Suk Lee","year":"2019","journal-title":"Innate Immun"},{"key":"2025122315374453200_vkaf206-B3","doi-asserted-by":"crossref","first-page":"746889","DOI":"10.3389\/fimmu.2022.746889","article-title":"Utilization of Treg cells in solid organ transplantation","volume":"13","author":"Juneja","year":"2022","journal-title":"Front Immunol"},{"key":"2025122315374453200_vkaf206-B4","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41573-021-00163-y","article-title":"Emerging concepts in the science of vaccine adjuvants","volume":"20","author":"Pulendran","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"2025122315374453200_vkaf206-B5","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrd1176","article-title":"Recent advances in the discovery and delivery of vaccine adjuvants","volume":"2","author":"O\u2019Hagan","year":"2003","journal-title":"Nat Rev Drug Discov"},{"key":"2025122315374453200_vkaf206-B6","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.immuni.2007.11.003","article-title":"How do adjuvants work? 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