Malherbe Delphine C, Messaoudi Ilhem
Department of Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, United States.
Front Immunol. 2022 Jun 29;13:911951. doi: 10.3389/fimmu.2022.911951. eCollection 2022.
Drinking alcohol, even in moderation, can affect the immune system. Studies have shown disproportionate effects of alcohol on circulating and tissue-resident myeloid cells (granulocytes, monocytes, macrophages, dendritic cells). These cells orchestrate the body's first line of defense against microbial challenges as well as maintain tissue homeostasis and repair. Alcohol's effects on these cells are dependent on exposure pattern, with acute drinking dampening but chronic drinking enhancing production of inflammatory mediators. Although chronic drinking is associated with heightened systemic inflammation, studies on tissue resident macrophage populations in several organs including the spleen, liver, brain, and lung have also shown compromised functional and metabolic capacities of these cells. Many of these effects are thought to be mediated by oxidative stress caused by alcohol and its metabolites which can directly impact the cellular epigenetic landscapes. In addition, since myeloid cells are relatively short-lived in circulation and are under constant repopulation from the bone marrow compartment, alcohol's effects on bone marrow progenitors and hematopoiesis are important for understanding the impact of alcohol systemically on these myeloid populations. Alcohol-induced disruption of progenitor, circulating, and tissue resident myeloid populations contribute to the increased susceptibility of patients with alcohol use disorders to viral and bacterial infections. In this review, we provide an overview of the impact of chronic alcohol consumption on the function of monocytes and macrophages in host defense, tissue repair and inflammation. We then summarize our current understanding of the mechanisms underlying alcohol-induced disruption and examine changes in transcriptome and epigenome of monocytes and mcrophages. Overall, chronic alcohol consumption leads to hyper-inflammation concomitant with decreased microbial and wound healing responses by monocytes/macrophages due to a rewiring of the epigentic and transcriptional landscape. However, in advanced alcoholic liver disease, myeloid cells become immunosuppressed as a response to the surrounding hyper-inflammatory milieu. Therefore, the effect of chronic alcohol on the inflammatory response depends on disease state and the immune cell population.
即使适度饮酒也会影响免疫系统。研究表明，酒精对循环系统和组织驻留髓样细胞（粒细胞、单核细胞、巨噬细胞、树突状细胞）有不同程度的影响。这些细胞协调身体抵御微生物挑战的第一道防线，并维持组织稳态和修复。酒精对这些细胞的影响取决于暴露模式，急性饮酒会抑制但慢性饮酒会增强炎症介质的产生。尽管慢性饮酒与全身炎症加剧有关，但对包括脾脏、肝脏、大脑和肺在内的多个器官中组织驻留巨噬细胞群体的研究也表明，这些细胞的功能和代谢能力受损。许多这些影响被认为是由酒精及其代谢产物引起的氧化应激介导的，氧化应激可直接影响细胞表观遗传格局。此外，由于髓样细胞在循环中寿命相对较短，并且不断从骨髓区室进行补充，酒精对骨髓祖细胞和造血作用的影响对于理解酒精对这些髓样群体的全身影响很重要。酒精引起的祖细胞、循环和组织驻留髓样群体的破坏导致酒精使用障碍患者对病毒和细菌感染的易感性增加。在这篇综述中，我们概述了慢性饮酒对单核细胞和巨噬细胞在宿主防御、组织修复和炎症中的功能的影响。然后，我们总结了目前对酒精诱导破坏的潜在机制以及单核细胞和巨噬细胞转录组和表观基因组变化的理解。总体而言，慢性饮酒会导致过度炎症，同时由于表观遗传和转录格局的重新布线，单核细胞/巨噬细胞的微生物和伤口愈合反应会降低。然而，在晚期酒精性肝病中，髓样细胞会因对周围高炎症环境的反应而受到免疫抑制。因此，慢性酒精对炎症反应的影响取决于疾病状态和免疫细胞群体。
