{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:47:56Z","timestamp":1787510876558,"version":"build-2736575974"},"reference-count":109,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Sepsis, which is characterized by potentially fatal multiple organ dysfunction, is caused by an abnormal host response to a major infection. During sepsis, the pathogen stimulates the host to activate resistance mechanisms that enhance immune cells\u2019 oxygen consumption in inflammatory tissues and cells, and promote aerobic glycolysis. Lactate generated by aerobic glycolysis is an essential substrate for the tricarboxylic acid cycle and for post-translational modifications via histone lactylation and epigenetic regulation. It also serves as a signaling molecule that modulates macrophage polarization between pro- and anti-inflammatory phenotypes in response to inflammatory and metabolic signals in their local environment. The roles of lactate and lactylation modifications in cancer cell proliferation and invasion have been well studied and are now potential therapeutic targets for various malignancies. However, the roles of lactate and lactylation modification in sepsis remain unclear. This review focuses on lactate\u2019s regulatory mechanism and lactylation modification during macrophage polarization in sepsis, and investigates whether this regulation could be a potential therapeutic target for sepsis.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1662444","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:19:23Z","timestamp":1768205963000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Lactate and lactylation in macrophage polarization of sepsis"],"prefix":"10.3389","volume":"15","author":[{"given":"Jian","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1042\/BST20140094","article-title":"Role of CoA and acetyl-CoA in regulating cardiac fatty acid and glucose oxidation","volume":"42","author":"Abo Alrob","year":"2014","journal-title":"Biochem. 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