Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens.
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.
Tan
Belinda H
BH
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Meinken
Christoph
C
Bastian
Max
M
Bruns
Heiko
H
Legaspi
Annaliza
A
Ochoa
Maria Teresa
MT
Krutzik
Stephan R
SR
Bloom
Barry R
BR
Ganz
Tomas
T
Modlin
Robert L
RL
Stenger
Steffen
S
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
D015415:Biomarkers; D006131:Growth Inhibitors; D023084:alpha-Defensins; C406413:human neutrophil peptide 1