Innate Immunity and Alcohol

Abstract

The innate immunity has evolved during millions of years, and thus, equivalent or comparable components are found in most vertebrates, invertebrates, and even plants. It constitutes the first line of defense against molecules, which are either pathogen-derived or a danger signal themselves, and not seldom both. These molecular patterns are comprised of highly conserved structures, a common trait in innate immunity, and constitute very potent triggers for inflammation mediated via extracellular or intracellular pattern recognition receptors. Human culture is often interweaved with the consumption of alcohol, in both drinking habits, its acute or chronical misuse. Apart from behavioral effects as often observed in intoxicated individuals, alcohol consumption also leads to immunological modulation on the humoral and cellular levels. In the last 20 years, major advances in this field of research have been made in clinical studies, as well as in vitro and in vivo research. As every physician will experience intoxicated patients, it is important to be aware of the changes that this cohort undergoes. This review will provide a summary of the current knowledge on the influence of alcohol consumption on certain factors of innate immunity after a hit, followed by the current studies that display the effect of alcohol with a description of the model, the mode of alcohol administration, as well as its dose. This will provide a way for the reader to evaluate the findings presented.

Keywords: DAMP; PAMP; alcohol; signaling; sterile inflammation.

Figure 1

Potential intracellular target points for (i) acute alcohol and (ii) chronic alcohol in a stylized cell. The induction of canonical NF-κB with p50–p65 translocation to nucleus via pattern recognition receptors (PRR) is outlined by, for example, TLR4 and MyD88 activation. The non-canonical NF-κB pathway with p52-RelB is detailed with CD40 as the respective receptor. Either pathway leads to the transcription of inflammatory cytokines (e.g., TNF-α or important immune regulatory proteins potentiating, for example, inflammasome formation.) Inflammasome formation itself is comprised of ASC, Caspase-1, and NLRP3 and regulated via ionic currents or intracellular PRRs, like nucleotide-binding oligomerization domain (NOD). Another cell compartment under alcohol influence is the phagosome needed for ingestion and destruction of pathogens using an array of reactive oxygen species.

Figure 2

Potential target points for (i) acute alcohol and (ii) chronic alcohol in inflammatory tissue. Neutrophils and monocytes migrate towards the site of inflammation via adhesion molecules like P-selectin and intercellular adhesion molecule (ICAM), which can be induced by activated macrophages. This process of transmigration is further enhanced by secretion of chemokines and PAMPs as well as DAMPs. The process of phagocytosis is shown as an example in macrophages that clear the tissue of pathogens and cell debris. Neutrophils also produce reactive oxygen species that damage pathogens, as well as healthy tissue, and enhance endothelium leakiness.