دورية أكاديمية
Plasma from patients with bacterial sepsis or severe COVID-19 induces suppressive myeloid cell production from hematopoietic progenitors in vitro
| العنوان: | Plasma from patients with bacterial sepsis or severe COVID-19 induces suppressive myeloid cell production from hematopoietic progenitors in vitro |
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| المؤلفون: | Reyes, Miguel, Filbin, Michael R., Bhattacharyya, Roby P., Sonny, Abraham, Mehta, Arnav, Billman, Kianna, Kays, Kyle R., Pinilla-Vera, Mayra, Benson, Maura E., Cosimi, Lisa A., Hung, Deborah T., Levy, Bruce D., Villani, Alexandra-Chloe, Sade-Feldman, Moshe, Baron, Rebecca M., Goldberg, Marcia B., Blainey, Paul C, Hacohen, Nir |
| المساهمون: | Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT |
| المصدر: | Science |
| بيانات النشر: | American Association for the Advancement of Science (AAAS) |
| سنة النشر: | 2021 |
| المجموعة: | DSpace@MIT (Massachusetts Institute of Technology) |
| الوصف: | Bacterial sepsis and severe COVID-19 share similar clinical manifestations and are both associated with dysregulation of the myeloid cell compartment. We previously reported an expanded CD14⁺ monocyte state, MS1, in patients with bacterial sepsis and validated expansion of this cell subpopulation in publicly available transcriptomics data. Here, using published datasets, we show that the gene expression program associated with MS1 correlated with sepsis severity and was up-regulated in monocytes from patients with severe COVID-19. To examine the ontogeny and function of MS1 cells, we developed a cellular model for inducing CD14⁺ MS1 monocytes from healthy bone marrow hematopoietic stem and progenitor cells (HSPCs). We found that plasma from patients with bacterial sepsis or COVID-19 induced myelopoiesis in HSPCs in vitro and expression of the MS1 gene program in monocytes and neutrophils that differentiated from these HSPCs. Furthermore, we found that plasma concentrations of IL-6, and to a lesser extent IL-10, correlated with increased myeloid cell output from HSPCs in vitro and enhanced expression of the MS1 gene program. We validated the requirement for these two cytokines to induce the MS1 gene program through CRISPR-Cas9 editing of their receptors in HSPCs. Using this cellular model system, we demonstrated that induced MS1 cells were broadly immunosuppressive and showed decreased responsiveness to stimulation with a synthetic RNA analog. Our in vitro study suggests a potential role for systemic cytokines in inducing myelopoiesis during severe bacterial or SARS-CoV-2 infection. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
| اللغة: | English |
| تدمد: | 1946-6234 1946-6242 |
| العلاقة: | http://dx.doi.org/10.1126/scitranslmed.abe9599Test; Science Translational Medicine; https://hdl.handle.net/1721.1/132634Test; Reyes, Miguel et al. "Plasma from patients with bacterial sepsis or severe COVID-19 induces suppressive myeloid cell production from hematopoietic progenitors in vitro." Science Translational Medicine 13, 598 (June 2021): eabe9599. |
| الإتاحة: | https://doi.org/10.1126/scitranslmed.abe9599Test https://hdl.handle.net/1721.1/132634Test |
| حقوق: | Creative Commons Attribution 4.0 International license ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.B78EC4BC |
| قاعدة البيانات: | BASE |
| تدمد: | 19466234 19466242 |
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