title: Innate Lymphocyte/Ly6C(hi) Monocyte Crosstalk Promotes Klebsiella Pneumoniae Clearance.
abstract: Increasing antibiotic resistance among bacterial pathogens has rendered some infections untreatable with available antibiotics. Klebsiella pneumoniae, a bacterial pathogen that has acquired high-level antibiotic resistance, is a common cause of pulmonary infections. Optimal clearance of K. pneumoniae from the host lung requires TNF and IL-17A. Herein, we demonstrate that inflammatory monocytes are rapidly recruited to the lungs of K. pneumoniae-infected mice and produce TNF, which markedly increases the frequency of IL-17-producing innate lymphoid cells. While pulmonary clearance of K. pneumoniae is preserved in neutrophil-depleted mice, monocyte depletion or TNF deficiency impairs IL-17A-dependent resolution of pneumonia. Monocyte-mediated bacterial uptake and killing is enhanced by ILC production of IL-17A, indicating that innate lymphocytes engage in a positive-feedback loop with monocytes that promotes clearance of pneumonia. Innate immune defense against a highly antibiotic-resistant bacterial pathogen depends on crosstalk between inflammatory monocytes and innate lymphocytes that is mediated by TNF and IL-17A.
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Keith
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
authors.forename: Dane W
authors.initials: DW
authors.lastname: Samilo
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Carter
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Leiner
authors.affiliation: Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Clinical Microbiology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: pamere@mskcc.org.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
mesh_terms: D000818:Animals; D007249:Inflammation / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha