title: Distinct Contributions of Neutrophils and CCR2+ Monocytes to Pulmonary Clearance of Different Klebsiella pneumoniae Strains.
abstract: Klebsiella pneumoniae is a common respiratory pathogen, with some strains having developed broad resistance to clinically available antibiotics. Humans can become infected with many different K. pneumoniae strains that vary in genetic background, antibiotic susceptibility, capsule composition, and mucoid phenotype. Genome comparisons have revealed differences between K. pneumoniae strains, but the impact of genomic variability on immune-mediated clearance of pneumonia remains unclear. Experimental studies of pneumonia in mice have used the rodent-adapted 43816 strain of K. pneumoniae and demonstrated that neutrophils are essential for optimal host defense. It remains unclear, however, whether CCR2(+) monocytes contribute to K. pneumoniae clearance from the lung. We selectively depleted neutrophils, CCR2(+) monocytes, or both from immunocompetent mice and determined susceptibility to infection by the 43816 strain and 4 newly isolated clinical K. pneumoniae strains. The clinical K. pneumoniae strains, including one carbapenem-resistant ST258 strain, are less virulent than 43816. Optimal clearance of each of the 5 strains required either neutrophils or CCR2(+) monocytes. Selective neutrophil depletion markedly worsened infection with K. pneumoniae strain 43816 and three clinical isolates but did not increase susceptibility of mice to infection with the carbapenem-resistant K. pneumoniae ST258 strain. Depletion of CCR2(+) monocytes delayed recovery from infection with each of the 5 K. pneumoniae strains, revealing a contribution of these cells to bacterial clearance from the lung. Our findings demonstrate strain-dependent variation in the contributions of neutrophils and CCR2(+) monocytes to clearance of K. pneumoniae pulmonary infection.
authors.affiliation: Immunology Program, Sloan Kettering Institute, New York, New York, USA Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Immunology Program, Sloan Kettering Institute, New York, New York, USA Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Carter
authors.affiliation: Immunology Program, Sloan Kettering Institute, New York, New York, USA Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Leiner
authors.affiliation: Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA Clinical Microbiology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Tang
authors.affiliation: Public Health Research Institute Center, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Public Health Research Institute Center, New Jersey Medical School-Rutgers, The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.affiliation: Immunology Program, Sloan Kettering Institute, New York, New York, USA Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA Clinical Microbiology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA pamere@mskcc.org.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007710:Klebsiella Infections / Q000276:immunology / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D054390:Receptors, CCR2 / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology*
chemical_list: C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2