title: Neutropenia exacerbates infection by Acinetobacter baumannii clinical isolates in a murine wound model.
abstract: The Gram negative coccobacillus Acinetobacter baumannii has become an increasingly prevalent cause of hospital-acquired infections in recent years. The majority of clinical A. baumannii isolates display high-level resistance to antimicrobials, which severely compromises our capacity to care for patients with A. baumannii disease. Neutrophils are of major importance in the host defense against microbial infections. However, the contribution of these cells of innate immunity in host resistance to cutaneous A. baumannii infection has not been directly investigated. Hence, we hypothesized that depletion of neutrophils increases severity of bacterial disease in an experimental A. baumannii murine wound model. In this study, the Ly-6G-specific monoclonal antibody (mAb), 1A8, was used to generate neutropenic mice and the pathogenesis of several A. baumannii clinical isolates on wounded cutaneous tissue was investigated. We demonstrated that neutrophil depletion enhances bacterial burden using colony forming unit determinations. Also, mAb 1A8 reduces global measurements of wound healing in A. baumannii-infected animals. Interestingly, histological analysis of cutaneous tissue excised from A. baumannii-infected animals treated with mAb 1A8 displays enhanced collagen deposition. Furthermore, neutropenia and A. baumannii infection alter pro-inflammatory cytokine release leading to severe microbial disease. Our findings provide a better understanding of the impact of these innate immune cells in controlling A. baumannii skin infections.
authors.affiliation: Department of Biomedical Sciences, Long Island University-Post Brookville, NY, USA.
authors.forename: Laryssa M
authors.initials: LM
authors.lastname: Grguric-Smith
authors.affiliation: Department of Biomedical Sciences, Long Island University-Post Brookville, NY, USA ; Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology Old Westbury, NY, USA.
authors.forename: Hiu H
authors.initials: HH
authors.lastname: Lee
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: Melissa B
authors.initials: MB
authors.lastname: Brennan
authors.affiliation: Department of Microbiology, Johns Hopkins School of Public Health Baltimore, MD, USA.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: DeLeon-Rodriguez
authors.affiliation: Centre for Molecular & Cellular Biology of Inflammation, Kings College London, UK.
authors.forename: Carolina
authors.initials: C
authors.lastname: Coelho
authors.affiliation: Montefiore Medical Center, Division of Dermatology, Department of Medicine Bronx, NY, USA.
authors.forename: George
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology Old Westbury, NY, USA.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
keywords: Acinetobacter baumannii; collagen; cytokines; neutropenia; wound healing