Transcriptional and Epigenetic Regulation of Monocyte and Macrophage Dysfunction by Chronic Alcohol Consumption

Abstract

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.

Editorial: differences in altered duodenal T‐cell immunology in alcoholic liver damage versus NAFLD

“…Duodenal CD8 + T resident memory (TRM) cells were most significantly altered, both in terms of numbers and function. This is an important finding, as most alterations that have previously been identified were in the macrophage population rather than in T‐cells 2,3 . There is, however, growing insight into the role of T‐cells in both ALD 4 and non‐alcoholic fatty liver disease.…”

“…This is an important finding, as most alterations that have previously been identified were in the macrophage population rather than in Tcells. 2,3 There is, however, growing insight into the role of T-cells in both ALD 4 and non-alcoholic fatty liver disease. Intestinal CD8 + TRM lymphocytes act as local gatekeepers to protect against microbial attachment and invasion and translocation of microbes and/or their products in the circulation.…”

Alcohol and the mechanisms of liver disease

“…The effects of alcohol on macrophage functions are complex and bidirectional. Alcohol can directly impair macrophage phagocytosis, reducing their ability to engulf and eliminate pathogens 36 . Alcohol can also decrease the production of cytokines such as IL‐17 and TNF‐α, which are important for macrophage activation and function 37,38 .…”

Intergenerational Perioperative Neurocognitive Disorder

“…Epigenetic modifications can persist for years and affect all body processes and functions, including neurogenesis, neuroplasticity, cognition, memory, and behavior [ 271 , 272 , 273 , 274 , 275 ]. Various environmental factors, such as stress, inflammation, endocrine-disrupting chemicals, alcohol, substances of abuse, anesthetic agents, and others, can initiate epigenetic modifications [ 271 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 ]. Furthermore, the frequency of epigenetic modifications may accelerate as people age—a phenomenon known as epigenetic drift [ 290 , 291 ].…”