CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens
Megakaryocytes (MKs) continuously produce platelets to support hemostasis and form a niche for hematopoietic stem cell maintenance in the bone marrow. MKs are also involved in inflammatory responses; however, the mechanism remains poorly understood. Using single-cell sequencing, we identified a CXCR...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/78662 |
| _version_ | 1797998477245939712 |
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| author | Jin Wang Jiayi Xie Daosong Wang Xue Han Minqi Chen Guojun Shi Linjia Jiang Meng Zhao |
| author_facet | Jin Wang Jiayi Xie Daosong Wang Xue Han Minqi Chen Guojun Shi Linjia Jiang Meng Zhao |
| author_sort | Jin Wang |
| collection | DOAJ |
| description | Megakaryocytes (MKs) continuously produce platelets to support hemostasis and form a niche for hematopoietic stem cell maintenance in the bone marrow. MKs are also involved in inflammatory responses; however, the mechanism remains poorly understood. Using single-cell sequencing, we identified a CXCR4 highly expressed MK subpopulation, which exhibited both MK-specific and immune characteristics. CXCR4high MKs interacted with myeloid cells to promote their migration and stimulate the bacterial phagocytosis of macrophages and neutrophils by producing TNFα and IL-6. CXCR4high MKs were also capable of phagocytosis, processing, and presenting antigens to activate T cells. Furthermore, CXCR4high MKs also egressed circulation and infiltrated into the spleen, liver, and lung upon bacterial infection. Ablation of MKs suppressed the innate immune response and T cell activation to impair the anti-bacterial effects in mice under the Listeria monocytogenes challenge. Using hematopoietic stem/progenitor cell lineage-tracing mouse lines, we show that CXCR4high MKs were generated from infection-induced emergency megakaryopoiesis in response to bacterial infection. Overall, we identify the CXCR4high MKs, which regulate host-defense immune response against bacterial infection. |
| first_indexed | 2024-04-11T10:49:24Z |
| format | Article |
| id | doaj.art-f6de94ecd30a4c80bab0cc2eb0ba1eb3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:49:24Z |
| publishDate | 2022-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f6de94ecd30a4c80bab0cc2eb0ba1eb32022-12-22T04:28:58ZengeLife Sciences Publications LtdeLife2050-084X2022-07-011110.7554/eLife.78662CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogensJin Wang0https://orcid.org/0000-0002-4924-1716Jiayi Xie1https://orcid.org/0000-0001-8977-6654Daosong Wang2https://orcid.org/0000-0002-4786-6202Xue Han3Minqi Chen4Guojun Shi5Linjia Jiang6https://orcid.org/0000-0001-8854-2610Meng Zhao7https://orcid.org/0000-0001-7909-7594Department of Endocrinology & Metabolism, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaRNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Ministry of Education, Guangzhou, ChinaKey Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Ministry of Education, Guangzhou, ChinaRNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Ministry of Education, Guangzhou, ChinaKey Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Ministry of Education, Guangzhou, ChinaDepartment of Endocrinology & Metabolism, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, ChinaRNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaRNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Stem Cells and Tissue Engineering, Zhongshan School of Medicine, Sun Yat-sen University, Ministry of Education, Guangzhou, ChinaMegakaryocytes (MKs) continuously produce platelets to support hemostasis and form a niche for hematopoietic stem cell maintenance in the bone marrow. MKs are also involved in inflammatory responses; however, the mechanism remains poorly understood. Using single-cell sequencing, we identified a CXCR4 highly expressed MK subpopulation, which exhibited both MK-specific and immune characteristics. CXCR4high MKs interacted with myeloid cells to promote their migration and stimulate the bacterial phagocytosis of macrophages and neutrophils by producing TNFα and IL-6. CXCR4high MKs were also capable of phagocytosis, processing, and presenting antigens to activate T cells. Furthermore, CXCR4high MKs also egressed circulation and infiltrated into the spleen, liver, and lung upon bacterial infection. Ablation of MKs suppressed the innate immune response and T cell activation to impair the anti-bacterial effects in mice under the Listeria monocytogenes challenge. Using hematopoietic stem/progenitor cell lineage-tracing mouse lines, we show that CXCR4high MKs were generated from infection-induced emergency megakaryopoiesis in response to bacterial infection. Overall, we identify the CXCR4high MKs, which regulate host-defense immune response against bacterial infection.https://elifesciences.org/articles/78662hematopoietic stem cellhost-defense immunitymegakaryocytesmegakaryopoiesis |
| spellingShingle | Jin Wang Jiayi Xie Daosong Wang Xue Han Minqi Chen Guojun Shi Linjia Jiang Meng Zhao CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens eLife hematopoietic stem cell host-defense immunity megakaryocytes megakaryopoiesis |
| title | CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens |
| title_full | CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens |
| title_fullStr | CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens |
| title_full_unstemmed | CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens |
| title_short | CXCR4high megakaryocytes regulate host-defense immunity against bacterial pathogens |
| title_sort | cxcr4high megakaryocytes regulate host defense immunity against bacterial pathogens |
| topic | hematopoietic stem cell host-defense immunity megakaryocytes megakaryopoiesis |
| url | https://elifesciences.org/articles/78662 |
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