DNA flowerstructure co-localizes with human pathogens in infected macrophages

Oskar Franch, Camino Gutiérrez-Corbo, Bárbara Domínguez-Asenjo, Thomas Boesen, Pia Bomholt Jensen, Lene N Nejsum, Josephine Geertsen Keller, Simon Pagaard Nielsen, Prakruti R Singh, Rajiv Kumar Jha, Valakunja Nagaraja, Rafael Balaña-Fouce, Yi-Ping Ho, Rosa María Reguera, Birgitta Ruth Knudsen

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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.

OriginalsprogEngelsk
TidsskriftNucleic Acids Research
Vol/bind48
Nummer11
Sider (fra-til)6081-6091
Antal sider11
ISSN0305-1048
DOI
StatusUdgivet - jun. 2020

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