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To investigate the potential role of the bacterial metabolite desaminotyrosine (DAT) in regulating host defense and inflammation, we pretreated mouse bone marrow\u2010derived macrophages (BMDMs) with DAT for 12\u2009hours and then challenged with bacterial lipopolysaccharide (LPS). We found that DAT priming\u2010enhanced type I interferon response while selectively inhibiting proinflammatory interleukin (IL)\u20106 production after exposure to LPS. This is related to the fact that DAT is a natural antioxidant determined by radical scavenging assay in a cell\u2010free system. DAT\u2010primed cells had increased levels of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) upon LPS stimulation. Countering the increased NADPH by supplementing extra oxidized NADP\n                    <jats:sup>+<\/jats:sup>\n                    to cells reversed DAT's effect on LPS\u2010induced\n                    <jats:italic>Il\u20106<\/jats:italic>\n                    and interferon\u2010stimulated gene expressions. DAT\u2010primed cells also were more resistant to oxidative stress\u2010induced generation of reactive oxygen species and cell death. DAT promoted the production of antimicrobial effector nitric oxide in a cellular redox\u2010dependent manner, leading to enhanced macrophage antimicrobial activity during\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    infection. Our data suggest that DAT acts as a host\u2010microbiota crosstalk signal in shaping host immune defense and inflammatory response.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400638r","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T10:28:54Z","timestamp":1721816934000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Desaminotyrosine is a redox\u2010active microbial metabolite that bolsters macrophage antimicrobial functions while attenuating\n                    <scp>IL<\/scp>\n                    \u20106 production"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-0781","authenticated-orcid":false,"given":"Junyang","family":"Zhou","sequence":"first","affiliation":[{"name":"Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology Xuzhou Medical 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