Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain
Retrotransposon Gag-like (RTL) genes play a variety of essential and important roles in the eutherian placenta and brain. It has recently been demonstrated that <i>RTL5</i> and <i>RTL6</i> (also known as <i>sushi-ichi retrotransposon homolog 8</i> (<i>SIRH8&...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14884 |
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| author | Fumitoshi Ishino Johbu Itoh Masahito Irie Ayumi Matsuzawa Mie Naruse Toru Suzuki Yuichi Hiraoka Tomoko Kaneko-Ishino |
| author_facet | Fumitoshi Ishino Johbu Itoh Masahito Irie Ayumi Matsuzawa Mie Naruse Toru Suzuki Yuichi Hiraoka Tomoko Kaneko-Ishino |
| author_sort | Fumitoshi Ishino |
| collection | DOAJ |
| description | Retrotransposon Gag-like (RTL) genes play a variety of essential and important roles in the eutherian placenta and brain. It has recently been demonstrated that <i>RTL5</i> and <i>RTL6</i> (also known as <i>sushi-ichi retrotransposon homolog 8</i> (<i>SIRH8</i>) and <i>SIRH3</i>) are microglial genes that play important roles in the brain’s innate immunity against viruses and bacteria through their removal of double-stranded RNA and lipopolysaccharide, respectively. In this work, we addressed the function of <i>RTL9</i> (also known as <i>SIRH10</i>). Using knock-in mice that produce RTL9-mCherry fusion protein, we examined RTL9 expression in the brain and its reaction to fungal zymosan. Here, we demonstrate that <i>RTL9</i> plays an important role, degrading zymosan in the brain. The RTL9 protein is localized in the microglial lysosomes where incorporated zymosan is digested. Furthermore, in <i>Rtl9</i> knockout mice expressing RTL9ΔC protein lacking the C-terminus retroviral GAG-like region, the zymosan degrading activity was lost. Thus, RTL9 is essentially engaged in this reaction, presumably via its GAG-like region. Together with our previous study, this result highlights the importance of three retrovirus-derived microglial RTL genes as eutherian-specific constituents of the current brain innate immune system: <i>RTL9</i>, <i>RTL5</i> and <i>RTL6</i>, responding to fungi, viruses and bacteria, respectively. |
| first_indexed | 2024-03-10T21:42:35Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:42:35Z |
| publishDate | 2023-10-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-43106cf511f04d9ba445b029fbbd42cf2023-11-19T14:32:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124191488410.3390/ijms241914884Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian BrainFumitoshi Ishino0Johbu Itoh1Masahito Irie2Ayumi Matsuzawa3Mie Naruse4Toru Suzuki5Yuichi Hiraoka6Tomoko Kaneko-Ishino7Department of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, JapanDepartment of Pathology, School of Medicine, Tokai University, Isehara 259-1193, JapanDepartment of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, JapanDepartment of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, JapanDepartment of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, JapanLaboratory of Genome Editing for Biomedical Research, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, JapanLaboratory of Genome Editing for Biomedical Research, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, JapanFaculty of Nursing, School of Medicine, Tokai University, Isehara 259-1193, JapanRetrotransposon Gag-like (RTL) genes play a variety of essential and important roles in the eutherian placenta and brain. It has recently been demonstrated that <i>RTL5</i> and <i>RTL6</i> (also known as <i>sushi-ichi retrotransposon homolog 8</i> (<i>SIRH8</i>) and <i>SIRH3</i>) are microglial genes that play important roles in the brain’s innate immunity against viruses and bacteria through their removal of double-stranded RNA and lipopolysaccharide, respectively. In this work, we addressed the function of <i>RTL9</i> (also known as <i>SIRH10</i>). Using knock-in mice that produce RTL9-mCherry fusion protein, we examined RTL9 expression in the brain and its reaction to fungal zymosan. Here, we demonstrate that <i>RTL9</i> plays an important role, degrading zymosan in the brain. The RTL9 protein is localized in the microglial lysosomes where incorporated zymosan is digested. Furthermore, in <i>Rtl9</i> knockout mice expressing RTL9ΔC protein lacking the C-terminus retroviral GAG-like region, the zymosan degrading activity was lost. Thus, RTL9 is essentially engaged in this reaction, presumably via its GAG-like region. Together with our previous study, this result highlights the importance of three retrovirus-derived microglial RTL genes as eutherian-specific constituents of the current brain innate immune system: <i>RTL9</i>, <i>RTL5</i> and <i>RTL6</i>, responding to fungi, viruses and bacteria, respectively.https://www.mdpi.com/1422-0067/24/19/14884retrovirus-derived gene <i>RTL9</i>fungibrain innate immunitymicrogliazymosanlysosome |
| spellingShingle | Fumitoshi Ishino Johbu Itoh Masahito Irie Ayumi Matsuzawa Mie Naruse Toru Suzuki Yuichi Hiraoka Tomoko Kaneko-Ishino Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain International Journal of Molecular Sciences retrovirus-derived gene <i>RTL9</i> fungi brain innate immunity microglia zymosan lysosome |
| title | Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain |
| title_full | Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain |
| title_fullStr | Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain |
| title_full_unstemmed | Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain |
| title_short | Retrovirus-Derived <i>RTL9</i> Plays an Important Role in Innate Antifungal Immunity in the Eutherian Brain |
| title_sort | retrovirus derived i rtl9 i plays an important role in innate antifungal immunity in the eutherian brain |
| topic | retrovirus-derived gene <i>RTL9</i> fungi brain innate immunity microglia zymosan lysosome |
| url | https://www.mdpi.com/1422-0067/24/19/14884 |
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