LL37:DNA complexes provide antimicrobial activity against intracellular bacteria in human macrophages |
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| Authors: | Alexander Stephan Marina Batinica Julia Steiger Pia Hartmann Frank Zaucke Wilhelm Bloch Mario Fabri |
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| Institution: | 1. Department of Dermatology, University of Cologne, Cologne, Germany;2. 1st Department of Internal Medicine, University of Cologne, Cologne, Germany;3. German Centre for Infection Research (DZIF), partner site Bonn‐Cologne, Cologne, Germany;4. Institute for Medical Microbiology, Immunology and Hygiene (IMMIH), University of Cologne, Cologne, Germany;5. Department of Hospital Hygiene and Infection Control, University of Cologne, Cologne, Germany;6. Centre for Biochemistry, University of Cologne, Cologne, Germany;7. Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany;8. Centre for Molecular Medicine, University of Cologne, Cologne, Germany |
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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. |
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| Keywords: | cathelicidin LL37 macrophage mycobacteria neutrophil extracellular trap |
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