DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> 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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/6/828 |
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| author | Adrianna Banducci-Karp Jiajun Xie Sem A. G. Engels Christos Sarantaris Patrick van Hage Monica Varela Annemarie H. Meijer Michiel van der Vaart |
| author_facet | Adrianna Banducci-Karp Jiajun Xie Sem A. G. Engels Christos Sarantaris Patrick van Hage Monica Varela Annemarie H. Meijer Michiel van der Vaart |
| author_sort | Adrianna Banducci-Karp |
| collection | DOAJ |
| 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 <i>Mycobacterium marinum</i> 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. |
| first_indexed | 2024-03-11T06:48:12Z |
| format | Article |
| id | doaj.art-fe9a02bba9f8417287cf604303a30a51 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T06:48:12Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fe9a02bba9f8417287cf604303a30a512023-11-17T10:12:25ZengMDPI AGCells2073-44092023-03-0112682810.3390/cells12060828DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> in MacrophagesAdrianna Banducci-Karp0Jiajun Xie1Sem A. G. Engels2Christos Sarantaris3Patrick van Hage4Monica Varela5Annemarie H. Meijer6Michiel van der Vaart7Institute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsDamage-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 <i>Mycobacterium marinum</i> 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.https://www.mdpi.com/2073-4409/12/6/828DRAM1innate immunitylysosomesmacrophagesmycobacteriumphagosomes |
| spellingShingle | Adrianna Banducci-Karp Jiajun Xie Sem A. G. Engels Christos Sarantaris Patrick van Hage Monica Varela Annemarie H. Meijer Michiel van der Vaart DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> in Macrophages Cells DRAM1 innate immunity lysosomes macrophages mycobacterium phagosomes |
| title | DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> in Macrophages |
| title_full | DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> in Macrophages |
| title_fullStr | DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> in Macrophages |
| title_full_unstemmed | DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> in Macrophages |
| title_short | DRAM1 Promotes Lysosomal Delivery of <i>Mycobacterium marinum</i> in Macrophages |
| title_sort | dram1 promotes lysosomal delivery of i mycobacterium marinum i in macrophages |
| topic | DRAM1 innate immunity lysosomes macrophages mycobacterium phagosomes |
| url | https://www.mdpi.com/2073-4409/12/6/828 |
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