Stephan, Alexander, Batinica, Marina, Steiger, Julia, Hartmann, Pia, Zaucke, Frank, Bloch, Wilhelm and Fabri, Mario (2016). LL37:DNA complexes provide antimicrobial activity against intracellular bacteria in human macrophages. Immunology, 148 (4). S. 420 - 433. HOBOKEN: WILEY. ISSN 1365-2567

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Abstract

As part of the innate host response neutrophils release neutrophil extracellular traps (NETs), protein:DNA complexes that contain a number of antimicrobial peptides (AMPs), such as cathelicidin. Human cathelicidin in its active form, LL37, has potent antimicrobial activity against bacteria. However, whether LL37 derived from NETs contributes to antimicrobial activity against intracellular pathogens remains unclear. Here, we report that NETs induced by mycobacteria contain cathelicidin. Human macrophages internalized NET-bound cathelicidin, which is transported to lysosomal compartments. Furthermore, using a model of in vitro-generated LL37:DNA complexes we found that LL37 derived from such complexes attacks mycobacteria in macrophage phagolysosomes resulting in antimicrobial activity. Taken together, our results suggest a mechanism by which LL37 in complex with DNA contributes to host defence against intracellular bacteria in human macrophages.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Stephan, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Batinica, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steiger, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, PiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zaucke, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloch, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fabri, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-267887
DOI: 10.1111/imm.12620
Journal or Publication Title: Immunology
Volume: 148
Number: 4
Page Range: S. 420 - 433
Date: 2016
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1365-2567
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NEUTROPHIL EXTRACELLULAR TRAPS; HUMAN CATHELICIDIN; PEPTIDE LL-37; MYCOBACTERIUM-TUBERCULOSIS; NETTING NEUTROPHILS; P2X(7) RECEPTOR; DENDRITIC CELLS; DNASE-II; DEGRADATION; MYELOPEROXIDASEMultiple languages
ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26788

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