Franch, O and Gutiérrez-Corbo, C and DomÃnguez-Asenjo, B and Boesen, T and Jensen, PB and Nejsum, LN and Keller, JG and Nielsen, SP and Singh, PR and Jha, RK and Nagaraja, V and Balaña-Fouce, R and Ho, Y-P and Reguera, RM and Knudsen, BR (2020) DNA flowerstructure co-localizes with human pathogens in infected macrophages. In: Nucleic Acids Research, 48 (11). pp. 6081-6091.
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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 nontoxic 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. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
| Item Type: | Journal Article |
|---|---|
| Publication: | Nucleic Acids Research |
| Publisher: | Oxford University Press |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | animal cell; Article; C2C12 cell line; cell compartmentalization; cell labeling; cellular distribution; controlled study; DNA determination; DNA structure; female; flow cytometry; gene amplification; gene location; half life time; hydrodynamics; immune system; Leishmania infantum; macrophage; mouse; Mycobacterium tuberculosis; nonhuman; phagocytosis; phagolysosome; RAW 264.7 cell line; scanning electron microscopy; staining; THP-1 cell line; transmission electron microscopy; tuberculosis; chemistry; cytology; DNA replication; fluorescence; human; immunology; leishmaniasis; macrophage; metabolism; microbiology; nucleic acid amplification; parasitology; phagosome; tuberculosis, DNA; nanomaterial, DNA; DNA Replication; Fluorescence; Half-Life; Humans; Leishmania infantum; Leishmaniasis; Macrophages; Mycobacterium tuberculosis; Nanostructures; Nucleic Acid Amplification Techniques; Phagocytosis; Phagosomes; Tuberculosis |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 24 Jan 2023 04:37 |
| Last Modified: | 24 Jan 2023 04:37 |
| URI: | https://eprints.iisc.ac.in/id/eprint/79301 |
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