Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study
Abstract Background Sepsis is commonly associated with acute respiratory distress syndrome (ARDS). Although the exaggerated inflammation may damage intact lung tissues, a percentage of patients with ARDS are reportedly immunocompromised, with worse outcomes. Herein, using a murine sepsis model, time...
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SpringerOpen
2024-12-01
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| Series: | Intensive Care Medicine Experimental |
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| Online Access: | https://doi.org/10.1186/s40635-024-00707-7 |
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| author | Qiuming Meng Fumiko Seto Tokie Totsu Tomoyuki Miyashita Songfei Wu Masahiko Bougaki Michiko Ushio Takahiro Hiruma Bruce C. Trapnell Kanji Uchida |
| author_facet | Qiuming Meng Fumiko Seto Tokie Totsu Tomoyuki Miyashita Songfei Wu Masahiko Bougaki Michiko Ushio Takahiro Hiruma Bruce C. Trapnell Kanji Uchida |
| author_sort | Qiuming Meng |
| collection | DOAJ |
| description | Abstract Background Sepsis is commonly associated with acute respiratory distress syndrome (ARDS). Although the exaggerated inflammation may damage intact lung tissues, a percentage of patients with ARDS are reportedly immunocompromised, with worse outcomes. Herein, using a murine sepsis model, time-course immune reprogramming after sepsis was evaluated to explore whether the host is immunocompromised. Leukocyte kinetics in the lung tissue were evaluated in a male C57/BL6 mouse model of mild peritoneal sepsis induced by cecal ligation and puncture, with the survival rate exceeds 90%. Lung immune reactivity was evaluated by intratracheal instillation of lipopolysaccharide (LPS; 30 µg). Furthermore, the effect of interferon (IFN)-β in vivo and ex vivo was evaluated. Results Four days after sepsis, the lung water content remained high, even among mice in clinical recovery. While monocytes and neutrophils gradually accumulated in the lung interstitium, the inflammatory cytokine/chemokine expression levels in the lungs continued to decline. Intratracheal LPS instillation induced more leukocyte trafficking and protein leakage into the alveoli in the septic lung, indicating more severe lung injury. However, LPS stimulation-associated mRNA expression of tnf, il6, ccl2, and cxcl1 was suppressed. Intra-alveolar expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and keratinocyte-derived cytokine (KC) was also suppressed. Monocytes isolated from the lung tissue showed an impaired response in il6, ccl2, and cxcl1 to LPS. Systemic IFN-β restored the above impaired regulator function of monocytes, as did coculturing these cells from lung tissue with IFN-β. Conclusions Histologically accelerated inflammation and paradoxically suppressed immunological regulator signaling were observed in the early recovery phase of sepsis. This observation may provide a model for the immunologically irresponsive state that occurs in some patients with sepsis. Systemic IFN-β partly restored the post-septic immunocompromised state, indicating its therapeutic potential for the immunosuppressive state seen in some patients with sepsis/ARDS. |
| format | Article |
| id | doaj-art-923c0e4bf8d245519946b6d2b8b31ef2 |
| institution | Kabale University |
| issn | 2197-425X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | SpringerOpen |
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| series | Intensive Care Medicine Experimental |
| spelling | doaj-art-923c0e4bf8d245519946b6d2b8b31ef22024-12-22T12:07:54ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2024-12-0112111410.1186/s40635-024-00707-7Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model studyQiuming Meng0Fumiko Seto1Tokie Totsu2Tomoyuki Miyashita3Songfei Wu4Masahiko Bougaki5Michiko Ushio6Takahiro Hiruma7Bruce C. Trapnell8Kanji Uchida9Department of Anesthesiology, Graduate School of Medicine, The University of TokyoDepartment of Anesthesiology, Graduate School of Medicine, The University of TokyoDepartment of Anesthesiology, Graduate School of Medicine, The University of TokyoDepartment of Anesthesiology, Graduate School of Medicine, The University of TokyoDepartment of Anesthesiology, Graduate School of Medicine, The University of TokyoDepartment of Anesthesiology, Graduate School of Medicine, The University of TokyoDepartment of Anesthesiology, Graduate School of Medicine, The University of TokyoDepartment of Emergency and Intensive Care Medicine, Department of Emergency and Critical Care Medicine, Fukushima Medical University, Southern Tohoku Research Institute for Neuroscience, Southern Tohoku General HospitalDivision of Pulmonary Biology, Perinatal Institute, Cincinnati Children’s Hospital Medical CenterDepartment of Anesthesiology, Graduate School of Medicine, The University of TokyoAbstract Background Sepsis is commonly associated with acute respiratory distress syndrome (ARDS). Although the exaggerated inflammation may damage intact lung tissues, a percentage of patients with ARDS are reportedly immunocompromised, with worse outcomes. Herein, using a murine sepsis model, time-course immune reprogramming after sepsis was evaluated to explore whether the host is immunocompromised. Leukocyte kinetics in the lung tissue were evaluated in a male C57/BL6 mouse model of mild peritoneal sepsis induced by cecal ligation and puncture, with the survival rate exceeds 90%. Lung immune reactivity was evaluated by intratracheal instillation of lipopolysaccharide (LPS; 30 µg). Furthermore, the effect of interferon (IFN)-β in vivo and ex vivo was evaluated. Results Four days after sepsis, the lung water content remained high, even among mice in clinical recovery. While monocytes and neutrophils gradually accumulated in the lung interstitium, the inflammatory cytokine/chemokine expression levels in the lungs continued to decline. Intratracheal LPS instillation induced more leukocyte trafficking and protein leakage into the alveoli in the septic lung, indicating more severe lung injury. However, LPS stimulation-associated mRNA expression of tnf, il6, ccl2, and cxcl1 was suppressed. Intra-alveolar expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and keratinocyte-derived cytokine (KC) was also suppressed. Monocytes isolated from the lung tissue showed an impaired response in il6, ccl2, and cxcl1 to LPS. Systemic IFN-β restored the above impaired regulator function of monocytes, as did coculturing these cells from lung tissue with IFN-β. Conclusions Histologically accelerated inflammation and paradoxically suppressed immunological regulator signaling were observed in the early recovery phase of sepsis. This observation may provide a model for the immunologically irresponsive state that occurs in some patients with sepsis. Systemic IFN-β partly restored the post-septic immunocompromised state, indicating its therapeutic potential for the immunosuppressive state seen in some patients with sepsis/ARDS.https://doi.org/10.1186/s40635-024-00707-7SepsisAcute lung injuryARDSInnate immunityImmune suppressionImmune reprogramming |
| spellingShingle | Qiuming Meng Fumiko Seto Tokie Totsu Tomoyuki Miyashita Songfei Wu Masahiko Bougaki Michiko Ushio Takahiro Hiruma Bruce C. Trapnell Kanji Uchida Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study Intensive Care Medicine Experimental Sepsis Acute lung injury ARDS Innate immunity Immune suppression Immune reprogramming |
| title | Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study |
| title_full | Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study |
| title_fullStr | Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study |
| title_full_unstemmed | Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study |
| title_short | Lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon: a mouse model study |
| title_sort | lung immune incompetency after mild peritoneal sepsis and its partial restoration by type 1 interferon a mouse model study |
| topic | Sepsis Acute lung injury ARDS Innate immunity Immune suppression Immune reprogramming |
| url | https://doi.org/10.1186/s40635-024-00707-7 |
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