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

doi:10.1093/nar/gkaa341

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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7 Citations (Scopus)

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.

Original language	English
Journal	Nucleic Acids Research
Volume	48
Issue	11
Pages (from-to)	6081-6091
Number of pages	11
ISSN	0305-1048
DOIs	https://doi.org/10.1093/nar/gkaa341
Publication status	Published - Jun 2020

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Franch, O., Gutiérrez-Corbo, C., Domínguez-Asenjo, B., Boesen, T., Jensen, P. B., Nejsum, L. N., Keller, J. G., Nielsen, S. P., Singh, P. R., Jha, R. K., Nagaraja, V., Balaña-Fouce, R., Ho, Y.-P., Reguera, R. M., & Knudsen, B. R. (2020). DNA flowerstructure co-localizes with human pathogens in infected macrophages. Nucleic Acids Research, 48(11), 6081-6091. https://doi.org/10.1093/nar/gkaa341

@article{d2bd790fe24740569f4c9c1cd4b9eef4,

title = "DNA flowerstructure co-localizes with human pathogens in infected macrophages",

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.",

author = "Oskar Franch and Camino Guti{\'e}rrez-Corbo and B{\'a}rbara Dom{\'i}nguez-Asenjo and Thomas Boesen and Jensen, {Pia Bomholt} and Nejsum, {Lene N} and Keller, {Josephine Geertsen} and Nielsen, {Simon Pagaard} and Singh, {Prakruti R} and Jha, {Rajiv Kumar} and Valakunja Nagaraja and Rafael Bala{\~n}a-Fouce and Yi-Ping Ho and Reguera, {Rosa Mar{\'i}a} and Knudsen, {Birgitta Ruth}",

note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.",

year = "2020",

month = jun,

doi = "10.1093/nar/gkaa341",

language = "English",

volume = "48",

pages = "6081--6091",

journal = "Nucleic Acids Research",

issn = "0305-1048",

publisher = "Oxford University Press",

number = "11",

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Franch, O, Gutiérrez-Corbo, C, Domínguez-Asenjo, B, Boesen, T , Jensen, PB , Nejsum, LN , Keller, JG, Nielsen, SP, Singh, PR, Jha, RK, Nagaraja, V, Balaña-Fouce, R, Ho, Y-P, Reguera, RM & Knudsen, BR 2020, 'DNA flowerstructure co-localizes with human pathogens in infected macrophages', Nucleic Acids Research, vol. 48, no. 11, pp. 6081-6091. https://doi.org/10.1093/nar/gkaa341

DNA flowerstructure co-localizes with human pathogens in infected macrophages. / Franch, Oskar; Gutiérrez-Corbo, Camino; Domínguez-Asenjo, Bárbara et al.
In: Nucleic Acids Research, Vol. 48, No. 11, 06.2020, p. 6081-6091.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - DNA flowerstructure co-localizes with human pathogens in infected macrophages

AU - Franch, Oskar

AU - Gutiérrez-Corbo, Camino

AU - Domínguez-Asenjo, Bárbara

AU - Boesen, Thomas

AU - Jensen, Pia Bomholt

AU - Nejsum, Lene N

AU - Keller, Josephine Geertsen

AU - Nielsen, Simon Pagaard

AU - Singh, Prakruti R

AU - Jha, Rajiv Kumar

AU - Nagaraja, Valakunja

AU - Balaña-Fouce, Rafael

AU - Ho, Yi-Ping

AU - Reguera, Rosa María

AU - Knudsen, Birgitta Ruth

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85086523557&partnerID=8YFLogxK

U2 - 10.1093/nar/gkaa341

DO - 10.1093/nar/gkaa341

M3 - Journal article

C2 - 32402089

SN - 0305-1048

VL - 48

SP - 6081

EP - 6091

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 11

ER -

DNA flowerstructure co-localizes with human pathogens in infected macrophages

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