Chronic ethanol consumption compromises neutrophil function in acute pulmonary Aspergillus fumigatus infection

Abstract

Chronic ethanol consumption is a leading cause of mortality worldwide, with higher risks to develop pulmonary infections, including Aspergillus infections. Mechanisms underlying increased susceptibility to infections are poorly understood. Chronic ethanol consumption induced increased mortality rates, higher Aspergillus fumigatus burden and reduced neutrophil recruitment into the airways. Intravital microscopy showed decrease in leukocyte adhesion and rolling after ethanol consumption. Moreover, downregulated neutrophil activation and increased levels of serum CXCL1 in ethanol-fed mice induced internalization of CXCR2 receptor in circulating neutrophils. Bone marrow-derived neutrophils from ethanol-fed mice showed lower fungal clearance and defective reactive oxygen species production. Taken together, results showed that ethanol affects activation, recruitment, phagocytosis and killing functions of neutrophils, causing susceptibility to pulmonary A. fumigatus infection. This study establishes a new paradigm in innate immune response in chronic ethanol consumers.

Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression and Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1–Induced Acute Lung Injury in K18-hACE2 Transgenic Mice

“…Similar to the previous study, transgenic mice on normal diet instilled with S1SP displayed a decline in body weight, that began recovering 48 h later. However, in alcohol-exposed mice, S1SP produced a continuously declining body weight, in agreement with a recent study where loss of body weight was significantly higher in alcohol-treated mice infected with Aspergillus fumigatus compared to similarly infected mice that did not receive alcohol [ 20 ]. This also agrees with the observation that heavy alcohol drinkers are at risk for abnormal long-term weight loss [ 21 ].…”

“…Chronic alcohol ingestion disturbs both immunologic and nonimmunologic host defense mechanisms within the airway [ 28 ]. Neutrophil recruitment into the airways is reduced in alcohol exposed mice infected with A. fumigatus [ 20 ]. Importantly, no pathohistological differences between alcoholic and non-alcoholic groups were observed in the first two days after infection.…”

Role of Neutrophils on the Ocular Surface

“…Chronic alcohol drinking impairs normal neutrophil extracellular trap formation and phagocytosis [ 127 , 128 ], although single alcohol drinking exaggerates the neutrophil response to the microbiome [ 129 ]. Neutrophil activation and functions are suppressed by alcohol consumption through C-X-C chemokine ligand 1/C-X-C chemokine receptor type 2 [ 130 ]. Vitamin D has been reported to have an immunomodulatory function [ 131 ].…”

The Impact of Alcohol Use Disorder on Tuberculosis: A Review of the Epidemiology and Potential Immunologic Mechanisms

“…Its adverse effects impact the basic defense and barrier functions of the cilia and alveolar epithelium as well as the functions of specialized cells including alveolar macrophages and PMNs. For example, AUD inhibits neutrophil margination, influx from the peripheral circulation into the alveolar space, and subsequent pathogen clearance and killing during infection ( 92 , 94 – 96 ). Antigen-presenting cells (APCs) of the innate immune system, necessary for adaptive immune activation, have a decreased peripheral presence and impaired activity due to alcohol ( 97 , 98 ).…”