Alcohol Enhances Acinetobacter baumannii-Associated Pneumonia and Systemic Dissemination by Impairing Neutrophil Antimicrobial Activity in a Murine Model of Infection

Abstract

Acinetobacter baumannii (Ab) is a common cause of community-acquired pneumonia (CAP) in chronic alcoholics in tropical and sub-tropical climates and associated with a >50% mortality rate. Using a murine model of alcohol (EtOH) administration, we demonstrated that EtOH enhances Ab-mediated pneumonia leading to systemic infection. Although EtOH did not affect neutrophil recruitment to the lungs of treated mice, it decreased phagocytosis and killing of bacteria by these leukocytes leading to increased microbial burden and severity of disease. Moreover, we determined that mice that received EtOH prior to Ab infection were immunologically impaired, which was reflected in increased pulmonary inflammation, sequential dissemination to the liver and kidneys, and decreased survival. Furthermore, immunosuppression by EtOH was associated with deregulation of cytokine production in the organs of infected mice. This study establishes that EtOH impairs immunity in vivo exacerbating Ab infection and disease progression. The ability of Ab to cause disease in alcoholics warrants the study of its virulence mechanisms and host interactions.

Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome through a direct effect on neutrophil chemotaxis

“…Neutrophil depletion also restored the virulence of bacterial mutants that were attenuated for disease. These data support findings observed in mammalian hosts whereby depletion of neutrophils exacerbated A. baumannii infection (5,34), whereas macrophage depletion had a limited impact on disease (15).…”

Alcohol, aging, and innate immunity

“…Most studies report a diminished phagocytic capacity in neutrophils from rodents after chronic or binge alcohol ingestion [121,[149][150][151][152], despite two other studies suggesting binge alcohol ingestion has no effect on phagocytosis [153,154]. A few reports propose that the impaired phagocytosis by neutrophils in alcohol-treated animals may be due to lower expression levels of important receptors involved in phagocytosis [135,136,155].…”

“…A few reports propose that the impaired phagocytosis by neutrophils in alcohol-treated animals may be due to lower expression levels of important receptors involved in phagocytosis [135,136,155]. Interestingly, reports show that both chronic and binge alcohol exposure boosts the production of ROS by neutrophils [121,149,150,156]; yet, the ability of neutrophils to kill pathogens is lessened after both binge and chronic alcohol exposure, which may partially be due to their aforementioned compromised phagocytic capacity [150,157,158]. There are no reports to date regarding the effect of alcohol consumption on NET formation, but NET formation is blunted with advanced age, possibly because of poorer ROS production in neutrophils from aged humans and mice [88,89].…”

Chronic alcohol abuse affects the clinical course and outcome of community-acquired bacterial meningitis

“…However, since self-reporting survey methods may lead to underestimation of drinking levels this proportion could be even higher. This high prevalence of alcoholics among our patients might be a direct consequence of impaired immune response to bacterial pathogens related to chronic alcohol abuse (21)(22)(23)(24) . Thus, it is likely that alcoholism is a risk factor for the development of BM, much like for the bacterial pneumonia.…”