{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:55:57Z","timestamp":1773024957633,"version":"3.50.1"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alcohol use is prevalent in the United States (US), with ~80% of persons over 12 years old reporting alcohol consumption in 2023 and ~10% of those individuals developing alcohol use disorder (AUD). Acute and chronic alcohol consumption exert opposite effects on the immune system. Specifically, acute alcohol exposure (AAE), (3\u201316 hours of <jats:italic>in-vitro<\/jats:italic> treatment, one binge episode in humans, or one gavage feeding in mice) skews monocytes towards a hypo-inflammatory phenotype associated with reduced TNF\u03b1, IL-6, and MCP-1 production. In contrast, chronic alcohol consumption (CAC) (7 days of <jats:italic>in-vitro<\/jats:italic> treatment, 3\u201312 months of consumption in animal models, or humans with confirmed AUD diagnosis), shifts the functional, transcriptional, metabolic, and epigenetic landscapes of monocytes and their progenitors towards a hyper-inflammatory profile. Despite the extensive work investigating AAE and CAC, few studies have examined short-term drinking durations. We sought to bridge this gap by assessing monocytes after 6 months of ethanol consumption in a rhesus macaque model, which we considered short-term drinking. Understanding the longitudinal changes in monocytes\u2019 phenotype and function in the context of alcohol consumption could pave the way to identifying diagnostic biomarkers for disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To bridge this gap, we obtained peripheral blood mononucleated cells (PBMC) isolated from rhesus macaques before and after 6 months of daily ethanol consumption (&amp;gt;55% of intakes over 2.0 g\/kg\/day). Monocytes were analyzed using a combination of flow cytometry, single-cell RNA-sequencing (scRNAseq), ELISAs, and Cleavage Under Targets and Tagmentation (CUT&amp;amp;Tag).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our data show that 6 months of ethanol consumption rewires monocytes towards a hypo-inflammatory profile as evidenced by reduced cytokine production. scRNAseq analysis revealed distinct shifts in monocyte states\/clusters with ethanol consumption and LPS stimulation in line with a shift to a hypo-inflammatory state. These changes may be driven by reduced levels of H3k4me3, a histone modification shown to be deposited at promoter regions of genes involved in inflammation and pathogen response signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Overall, these data demonstrate that 6 months of daily heavy drinking attenuates inflammatory responses in monocytes via shifts in the epigenetic landscape.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1606092","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T04:11:33Z","timestamp":1750651893000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Short-term heavy drinking in a non-human primate model skews monocytes toward a hypo-inflammatory phenotype"],"prefix":"10.3389","volume":"16","author":[{"given":"Madison 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