DNA flowerstructure co-localizes with human pathogens in infected macrophages. Issue 11 (13th May 2020)

• Record Type: Journal Article
• Authors: Franch, Oskar; Gutiérrez-Corbo, Camino; Domínguez-Asenjo, Bárbara; Boesen, Thomas; Jensen, Pia Bomholt; Nejsum, Lene N; Keller, Josephine Geertsen; Nielsen, Simon Pagaard; Singh, Prakruti R; Jha, Rajiv Kumar; Nagaraja, Valakunja; Balaña-Fouce, Rafael; Ho, Yi-Ping; Reguera, Rosa María; Knudsen, Birgitta Ruth
• Is Part Of: Nucleic acids research. Volume 48:Issue 11(2020)
• Page Start: 6081
• Page End: 6091
• Publication Date: 2020-05-13
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkaa341
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Herein, we characterize the cellular uptake of a DNA structure generated by rolling circle DNA amplification. The structure, termed nanoflower, was fluorescently labeled by incorporation of ATTO488-dUTP allowing the intracellular localization to be followed. The nanoflower had a hydrodynamic diameter of approximately 300 nanometer and was non-toxic for all mammalian cell lines tested. It was internalized specifically by mammalian macrophages by phagocytosis within a few hours resulting in specific compartmentalization in phagolysosomes. Maximum uptake was observed after eight hours and the nanoflower remained stable in the phagolysosomes with a half-life of 12 h. Interestingly, the nanoflower co-localized with both Mycobacterium tuberculosis and Leishmania infantum within infected macrophages although these pathogens escape lysosomal degradation by affecting the phagocytotic pathway in very different manners. These results suggest an intriguing and overlooked potential application of DNA structures in targeted treatment of infectious diseases such as tuberculosis and leishmaniasis that are caused by pathogens that escape the human immune system by modifying macrophage biology.