Acinetobacter baumannii is a Gram-negative bacterium that opportunistically infects critically ill hospitalized patients with breaches in skin integrity and airway protection, leading to significant morbidity and mortality. Considering the paucity of well-established animal models of immunosuppression to study A. baumannii pathogenesis, we set out to characterize a murine model of immunosuppression using the alkylating agent cyclophosphamide (CYP). We hypothesized that CYP-induced immunosuppression would increase the susceptibility of C57BL/ 6 mice to developing A. baumannii-mediated pneumonia followed by systemic disease. We demonstrated that CYP intensified A. baumannii-mediated pulmonary disease, abrogated normal immune cell function and led to altered pro-inflammatory cytokine release. The development of an animal model that mimics A. baumannii infection onset in immunosuppressed individuals is crucial for generating novel approaches to patient care and improving public health strategies to decrease exposure to infection for individuals at risk.

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 (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. We demonstrated that exposure of J774.16 macrophage-like cells to physiological alcohol (etOh) concentrations decreased phagocytosis and killing of Ab. etOh-mediated macrophage phagocytosis dysfunction may be associated with reduced expression of GtPase-rhoa, a key regulator of the actin polymerization signaling cascade. etOh inhibited nitric oxide (NO) generation via inducible NO-synthase inactivation, which enhanced Ab survival within macrophages. additionally, etOh alters cytokine production resulting in a dysregulated immune response. this study is a proof of principle which establishes that etOh might exacerbate Ab infection and be an important factor enhancing caP in individuals at risk.