title: Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens.
abstract: A key target of many intracellular pathogens is the macrophage. Although macrophages can generate antimicrobial activity, neutrophils have been shown to have a key role in host defense, presumably by their preformed granules containing antimicrobial agents. Yet the mechanism by which neutrophils can mediate antimicrobial activity against intracellular pathogens such as Mycobacterium tuberculosis has been a long-standing enigma. We demonstrate that apoptotic neutrophils and purified granules inhibit the growth of extracellular mycobacteria. Phagocytosis of apoptotic neutrophils by macrophages results in decreased viability of intracellular M. tuberculosis. Concomitant with uptake of apoptotic neutrophils, granule contents traffic to early endosomes, and colocalize with mycobacteria. Uptake of purified granules alone decreased growth of intracellular mycobacteria. Therefore, the transfer of antimicrobial peptides from neutrophils to macrophages provides a cooperative defense strategy between innate immune cells against intracellular pathogens and may complement other pathways that involve delivery of antimicrobial peptides to macrophages.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Belinda H
authors.initials: BH
authors.lastname: Tan
authors.forename: Christoph
authors.initials: C
authors.lastname: Meinken
authors.forename: Max
authors.initials: M
authors.lastname: Bastian
authors.forename: Heiko
authors.initials: H
authors.lastname: Bruns
authors.forename: Annaliza
authors.initials: A
authors.lastname: Legaspi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ochoa
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Krutzik
authors.forename: Barry R
authors.initials: BR
authors.lastname: Bloom
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Steffen
authors.initials: S
authors.lastname: Stenger
mesh_terms: D017209:Apoptosis / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001770:Blood Bactericidal Activity / Q000276:immunology*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology*; D011992:Endosomes / Q000276:immunology / Q000382:microbiology; D005110:Extracellular Space / Q000276:immunology / Q000382:microbiology; D006131:Growth Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology*; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D023084:alpha-Defensins / Q000032:analysis
chemical_list: D015415:Biomarkers; D006131:Growth Inhibitors; D023084:alpha-Defensins; C406413:human neutrophil peptide 1