title: Characterization of a cyclophosphamide-induced murine model of immunosuppression to study Acinetobacter baumannii pathogenesis.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Long Island University-Post, Brookville, NY, USA.
authors.forename: Swetha
authors.initials: S
authors.lastname: Manepalli
authors.affiliation: Department of Biomedical Sciences, Long Island University-Post, Brookville, NY, USA.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Gandhi
authors.affiliation: Department of Biomedical Sciences, Long Island University-Post, Brookville, NY, USA.
authors.forename: Vaibhav V
authors.initials: VV
authors.lastname: Ekhar
authors.affiliation: Department of Biomedical Sciences, Long Island University-Post, Brookville, NY, USA.
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Asplund
authors.affiliation: PhD Program in Experimental Biology and Biomedicine, Centre for Neuroscience and Cell Biology of Coimbra and Institute of Microbiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Coelho
authors.affiliation: Department of Medicine (Division of Infectious Diseases), Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Biomedical Sciences, Long Island University-Post, Brookville, NY, USA.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
mesh_terms: D000151:Acinetobacter Infections / Q000473:pathology*; D040981:Acinetobacter baumannii / Q000472:pathogenicity*; D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000150:complications / Q000382:microbiology / Q000473:pathology; D018805:Sepsis / Q000382:microbiology / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide