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DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages

Damage-Regulated Autophagy Modulator 1 (DRAM1) is an infection-inducible membrane protein, whose function in the immune response is incompletely understood. Based on previous results in a zebrafish infection model, we have proposed that DRAM1 is a host resistance factor against intracellular mycobac...

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Autores principales: Banducci-Karp, Adrianna, Xie, Jiajun, Engels, Sem A. G., Sarantaris, Christos, van Hage, Patrick, Varela, Monica, Meijer, Annemarie H., van der Vaart, Michiel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047064/
https://www.ncbi.nlm.nih.gov/pubmed/36980169
http://dx.doi.org/10.3390/cells12060828
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author Banducci-Karp, Adrianna
Xie, Jiajun
Engels, Sem A. G.
Sarantaris, Christos
van Hage, Patrick
Varela, Monica
Meijer, Annemarie H.
van der Vaart, Michiel
author_facet Banducci-Karp, Adrianna
Xie, Jiajun
Engels, Sem A. G.
Sarantaris, Christos
van Hage, Patrick
Varela, Monica
Meijer, Annemarie H.
van der Vaart, Michiel
author_sort Banducci-Karp, Adrianna
collection PubMed
description Damage-Regulated Autophagy Modulator 1 (DRAM1) is an infection-inducible membrane protein, whose function in the immune response is incompletely understood. Based on previous results in a zebrafish infection model, we have proposed that DRAM1 is a host resistance factor against intracellular mycobacterial infection. To gain insight into the cellular processes underlying DRAM1-mediated host defence, here we studied the interaction of DRAM1 with Mycobacterium marinum in murine RAW264.7 macrophages. We found that, shortly after phagocytosis, DRAM1 localised in a punctate pattern to mycobacteria, which gradually progressed to full DRAM1 envelopment of the bacteria. Within the same time frame, DRAM1-positive mycobacteria colocalised with the LC3 marker for autophagosomes and LysoTracker and LAMP1 markers for (endo)lysosomes. Knockdown analysis revealed that DRAM1 is required for the recruitment of LC3 and for the acidification of mycobacteria-containing vesicles. A reduction in the presence of LAMP1 further suggested reduced fusion of lysosomes with mycobacteria-containing vesicles. Finally, we show that DRAM1 knockdown impairs the ability of macrophages to defend against mycobacterial infection. Together, these results support that DRAM1 promotes the trafficking of mycobacteria through the degradative (auto)phagolysosomal pathway. Considering its prominent effect on host resistance to intracellular infection, DRAM1 is a promising target for therapeutic modulation of the microbicidal capacity of macrophages.
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spelling pubmed-100470642023-03-29 DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages Banducci-Karp, Adrianna Xie, Jiajun Engels, Sem A. G. Sarantaris, Christos van Hage, Patrick Varela, Monica Meijer, Annemarie H. van der Vaart, Michiel Cells Article Damage-Regulated Autophagy Modulator 1 (DRAM1) is an infection-inducible membrane protein, whose function in the immune response is incompletely understood. Based on previous results in a zebrafish infection model, we have proposed that DRAM1 is a host resistance factor against intracellular mycobacterial infection. To gain insight into the cellular processes underlying DRAM1-mediated host defence, here we studied the interaction of DRAM1 with Mycobacterium marinum in murine RAW264.7 macrophages. We found that, shortly after phagocytosis, DRAM1 localised in a punctate pattern to mycobacteria, which gradually progressed to full DRAM1 envelopment of the bacteria. Within the same time frame, DRAM1-positive mycobacteria colocalised with the LC3 marker for autophagosomes and LysoTracker and LAMP1 markers for (endo)lysosomes. Knockdown analysis revealed that DRAM1 is required for the recruitment of LC3 and for the acidification of mycobacteria-containing vesicles. A reduction in the presence of LAMP1 further suggested reduced fusion of lysosomes with mycobacteria-containing vesicles. Finally, we show that DRAM1 knockdown impairs the ability of macrophages to defend against mycobacterial infection. Together, these results support that DRAM1 promotes the trafficking of mycobacteria through the degradative (auto)phagolysosomal pathway. Considering its prominent effect on host resistance to intracellular infection, DRAM1 is a promising target for therapeutic modulation of the microbicidal capacity of macrophages. MDPI 2023-03-07 /pmc/articles/PMC10047064/ /pubmed/36980169 http://dx.doi.org/10.3390/cells12060828 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Banducci-Karp, Adrianna
Xie, Jiajun
Engels, Sem A. G.
Sarantaris, Christos
van Hage, Patrick
Varela, Monica
Meijer, Annemarie H.
van der Vaart, Michiel
DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages
title DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages
title_full DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages
title_fullStr DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages
title_full_unstemmed DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages
title_short DRAM1 Promotes Lysosomal Delivery of Mycobacterium marinum in Macrophages
title_sort dram1 promotes lysosomal delivery of mycobacterium marinum in macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047064/
https://www.ncbi.nlm.nih.gov/pubmed/36980169
http://dx.doi.org/10.3390/cells12060828
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