An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent
Adult hematopoietic stem and progenitor cells (HSPCs) respond to bacterial infections by expansion to myeloid cells. Sepsis impairs this process by suppressing differentiation of stem cells subsequently contributing to an ineffective immune response. Whether the magnitude of HSPCs impairment in seps...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.708670/full |
| _version_ | 1818921767908933632 |
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| author | Tomasz Skirecki Susanne Drechsler Aldona Jeznach Grażyna Hoser Mohammad Jafarmadar Jerzy Kawiak Marcin F. Osuchowski |
| author_facet | Tomasz Skirecki Susanne Drechsler Aldona Jeznach Grażyna Hoser Mohammad Jafarmadar Jerzy Kawiak Marcin F. Osuchowski |
| author_sort | Tomasz Skirecki |
| collection | DOAJ |
| description | Adult hematopoietic stem and progenitor cells (HSPCs) respond to bacterial infections by expansion to myeloid cells. Sepsis impairs this process by suppressing differentiation of stem cells subsequently contributing to an ineffective immune response. Whether the magnitude of HSPCs impairment in sepsis is severity-dependent remains unknown. This study investigated dynamics of the HSPC immune-inflammatory response in the bone marrow, splenic, and blood compartments in moribund and surviving septic mice. The 12-week-old outbred CD-1 female mice (n=65) were subjected to a cecal ligation and puncture (CLP) sepsis, treated with antibiotics and fluid resuscitation, and stratified into predicted-to-die (P-DIE) and predicted-to-survive (P-SUR) cohorts for analysis. CLP strongly reduced the common myeloid and multipotent progenitors, short- and long-term hematopoietic stem cell (HSC) counts in the bone marrow; lineage−ckit+Sca-1+ and short-term HSC suppression was greater in P-DIE versus P-SUR mice. A profound depletion of the common myeloid progenitors occurred in the blood (by 75%) and spleen (by 77%) of P-DIE. In P-SUR, most common circulating HSPCs subpopulations recovered to baseline by 72 h post-CLP. Analysis of activated caspase-1/-3/-7 revealed an increased apoptotic (by 30%) but not pyroptotic signaling in the bone marrow HSCs of P-DIE mice. The bone marrow from P-DIE mice revealed spikes of IL-6 (by 5-fold), CXCL1/KC (15-fold), CCL3/MIP-1α (1.7-fold), and CCL2/MCP-1 (2.8-fold) versus P-SUR and control (TNF, IFN-γ, IL-1β, -5, -10 remained unaltered). Summarizing, our findings demonstrate that an early sepsis-induced impairment of myelopoiesis is strongly outcome-dependent but varies among compartments. It is suggestive that the HSCPC loss is at least partly due to an increased apoptosis but not pyroptosis. |
| first_indexed | 2024-12-20T01:42:53Z |
| format | Article |
| id | doaj.art-9fe7a355ef374a2783c561c8bb570ae7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T01:42:53Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9fe7a355ef374a2783c561c8bb570ae72022-12-21T19:57:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.708670708670An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-DependentTomasz Skirecki0Susanne Drechsler1Aldona Jeznach2Grażyna Hoser3Mohammad Jafarmadar4Jerzy Kawiak5Marcin F. Osuchowski6Laboratory of Flow Cytometry, Centre of Postgraduate Medical Education, Warsaw, PolandLudwig Boltzmann Institute for Experimental and Clinical Traumatology in the Allgemeine Unfallversicherungsanstalt (AUVA) Research Center, Vienna, AustriaLaboratory of Flow Cytometry, Centre of Postgraduate Medical Education, Warsaw, PolandLaboratory of Flow Cytometry, Centre of Postgraduate Medical Education, Warsaw, PolandLudwig Boltzmann Institute for Experimental and Clinical Traumatology in the Allgemeine Unfallversicherungsanstalt (AUVA) Research Center, Vienna, AustriaLaboratory of Flow Cytometry, Centre of Postgraduate Medical Education, Warsaw, PolandLudwig Boltzmann Institute for Experimental and Clinical Traumatology in the Allgemeine Unfallversicherungsanstalt (AUVA) Research Center, Vienna, AustriaAdult hematopoietic stem and progenitor cells (HSPCs) respond to bacterial infections by expansion to myeloid cells. Sepsis impairs this process by suppressing differentiation of stem cells subsequently contributing to an ineffective immune response. Whether the magnitude of HSPCs impairment in sepsis is severity-dependent remains unknown. This study investigated dynamics of the HSPC immune-inflammatory response in the bone marrow, splenic, and blood compartments in moribund and surviving septic mice. The 12-week-old outbred CD-1 female mice (n=65) were subjected to a cecal ligation and puncture (CLP) sepsis, treated with antibiotics and fluid resuscitation, and stratified into predicted-to-die (P-DIE) and predicted-to-survive (P-SUR) cohorts for analysis. CLP strongly reduced the common myeloid and multipotent progenitors, short- and long-term hematopoietic stem cell (HSC) counts in the bone marrow; lineage−ckit+Sca-1+ and short-term HSC suppression was greater in P-DIE versus P-SUR mice. A profound depletion of the common myeloid progenitors occurred in the blood (by 75%) and spleen (by 77%) of P-DIE. In P-SUR, most common circulating HSPCs subpopulations recovered to baseline by 72 h post-CLP. Analysis of activated caspase-1/-3/-7 revealed an increased apoptotic (by 30%) but not pyroptotic signaling in the bone marrow HSCs of P-DIE mice. The bone marrow from P-DIE mice revealed spikes of IL-6 (by 5-fold), CXCL1/KC (15-fold), CCL3/MIP-1α (1.7-fold), and CCL2/MCP-1 (2.8-fold) versus P-SUR and control (TNF, IFN-γ, IL-1β, -5, -10 remained unaltered). Summarizing, our findings demonstrate that an early sepsis-induced impairment of myelopoiesis is strongly outcome-dependent but varies among compartments. It is suggestive that the HSCPC loss is at least partly due to an increased apoptosis but not pyroptosis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.708670/fullinfectioncecal ligation and puncturehematopoietic stem and progenitor cellsoutcome predictionimmunitycaspases |
| spellingShingle | Tomasz Skirecki Susanne Drechsler Aldona Jeznach Grażyna Hoser Mohammad Jafarmadar Jerzy Kawiak Marcin F. Osuchowski An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent Frontiers in Immunology infection cecal ligation and puncture hematopoietic stem and progenitor cells outcome prediction immunity caspases |
| title | An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent |
| title_full | An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent |
| title_fullStr | An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent |
| title_full_unstemmed | An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent |
| title_short | An Early Myelosuppression in the Acute Mouse Sepsis Is Partly Outcome-Dependent |
| title_sort | early myelosuppression in the acute mouse sepsis is partly outcome dependent |
| topic | infection cecal ligation and puncture hematopoietic stem and progenitor cells outcome prediction immunity caspases |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.708670/full |
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