Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge

Abstract

Alcohol abuse has been associated with increased susceptibility to pulmonary infection. It is not fully defined how alcohol contributes to the host defense compromise. Here primary human airway epithelial cells were cultured at an air-liquid interface to form a differentiated and polarized epithelium. This unique culture model allowed us to closely mimic lung infection in the context of alcohol abuse by basolateral alcohol exposure and apical live bacterial challenge. Application of clinically relevant concentrations of alcohol for 24 hours did not significantly alter epithelial integrity or barrier function. When apically challenged with viable Klebsiella pneumoniae, the cultured epithelia had an enhanced tightness which was unaffected by alcohol. Further, alcohol enhanced apical bacterial growth, but not bacterial binding to the cells. The cultured epithelium in the absence of any treatment or stimulation had a base-level IL-6 and IL-8 secretion. Apical bacterial challenge significantly elevated the basolateral secretion of inflammatory cytokines including IL-2, IL-4, IL-6, IL-8, IFN-γ, GM-CSF, and TNF-α. However, alcohol suppressed the observed cytokine burst in response to infection. Addition of adenosine receptor agonists negated the suppression of IL-6 and TNF-α. Thus, acute alcohol alters the epithelial cytokine response to infection, which can be partially mitigated by adenosine receptor agonists.

TLR2 and TLR4 Expression and Inflammatory Cytokines are Altered in the Airway Epithelium of Those with Alcohol Use Disorders

“…Our finding of increased IL‐6 and IL‐8 in the bronchial component of that BAL was initially surprising, because most in vitro models of airway epithelial alcohol exposure do not conclusively demonstrate differences in basal cytokine production with alcohol treatment alone (Bailey et al., ; Raju et al., ), but rather, after stimulation with bacterial products. It is worthwhile noting that human airways in vivo, such as those we examined, are continuously exposed to bacterial products through breathing, while in vitro models remain sterile, which may explain our observations.…”

Altered gut microbe metabolites in patients with alcohol‑induced osteonecrosis of the femoral head: An integrated omics analysis

“…Klebsiella and Streptococcus form another two members of the Proteobacteria phylum family. Individuals who consume excessive amounts of alcohol have previously been found to exhibit increased susceptibility to lung infection by Streptococcus pneumoniae and Klebsiella pneumoniae ( 37 ). Yuan et al ( 38 ) reported that ≤60% of individuals with non-alcoholic fatty liver disease in a Chinese cohort were infected with Klebsiella pneumoniae , a bacterial strain that produces alcohol as a byproduct of glucose.…”

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