Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions
Sepsis is characterized by a concomitant early pro-inflammatory response by immune cells to an infection, and an opposing anti-inflammatory response that results in protracted immunosuppression. The primary pathological event in sepsis is widespread programmed cell death, or cellular self-sacrifice,...
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| Format: | Article |
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493214/full |
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| author | Md. Monirul Islam Md. Monirul Islam Eizo Watanabe Umme Salma Masayuki Ozaki Takayuki Irahara Subaru Tanabe Ryusuke Katsuki Dai Oishi Naoshi Takeyama |
| author_facet | Md. Monirul Islam Md. Monirul Islam Eizo Watanabe Umme Salma Masayuki Ozaki Takayuki Irahara Subaru Tanabe Ryusuke Katsuki Dai Oishi Naoshi Takeyama |
| author_sort | Md. Monirul Islam |
| collection | DOAJ |
| description | Sepsis is characterized by a concomitant early pro-inflammatory response by immune cells to an infection, and an opposing anti-inflammatory response that results in protracted immunosuppression. The primary pathological event in sepsis is widespread programmed cell death, or cellular self-sacrifice, of innate and adaptive immune cells, leading to profound immunological suppression. This severe immune dysfunction hampers effective primary pathogen clearance, thereby increasing the risk of secondary opportunistic infections, latent viral reactivation, multiple organ dysfunction, and elevated mortality. The types of cell death include apoptosis (type I programmed cell death), autophagy (type II programmed cell death), NETosis (a program for formation of neutrophil extracellular traps (NETs)) and other programmed cell deaths like pyroptosis, ferroptosis, necroptosis, each contributing to immunosuppression in distinct ways during the later phases of sepsis. Extensive apoptosis of lymphocytes, such as CD4+, CD8+ T cells, and B cells, is strongly associated with immunosuppression. Apoptosis of dendritic cells further compromises T and B cell survival and can induce T cell anergy or promote regulatory Treg cell proliferation. Moreover, delayed apoptosis and impaired neutrophil function contribute to nosocomial infections and immune dysfunction in sepsis. Interestingly, aberrant NETosis and the subsequent depletion of mature neutrophils also trigger immunosuppression, and neutrophil pyroptosis can positively regulate NETosis. The interaction between programmed cell death 1 (PD-1) or programmed cell death 1 ligand (PD-L1) plays a key role in T cell modulation and neutrophil apoptosis in sepsis. The dendritic cell growth factor, Fms-like tyrosine kinase (FLTEL), increases DC numbers, enhances CD 28 expression, attenuates PD-L1, and improves survival in sepsis. Recently, immunoadjuvant therapies have attracted attention for their potential to restore host physiological immunity and homeostasis in patients with sepsis. This review focuses on several potential immunotherapeutic agents designed to bolster suppressed innate and adaptive immune responses in the management of sepsis. |
| format | Article |
| id | doaj-art-a74b6b0a55e0465faf7fcd4574cba098 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a74b6b0a55e0465faf7fcd4574cba0982024-12-10T05:10:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.14932141493214Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directionsMd. Monirul Islam0Md. Monirul Islam1Eizo Watanabe2Umme Salma3Masayuki Ozaki4Takayuki Irahara5Subaru Tanabe6Ryusuke Katsuki7Dai Oishi8Naoshi Takeyama9Department of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Biochemistry and Biotechnology, University of Science and Technology Chittagong (USTC), Chattogram, BangladeshDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanDepartment of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, JapanSepsis is characterized by a concomitant early pro-inflammatory response by immune cells to an infection, and an opposing anti-inflammatory response that results in protracted immunosuppression. The primary pathological event in sepsis is widespread programmed cell death, or cellular self-sacrifice, of innate and adaptive immune cells, leading to profound immunological suppression. This severe immune dysfunction hampers effective primary pathogen clearance, thereby increasing the risk of secondary opportunistic infections, latent viral reactivation, multiple organ dysfunction, and elevated mortality. The types of cell death include apoptosis (type I programmed cell death), autophagy (type II programmed cell death), NETosis (a program for formation of neutrophil extracellular traps (NETs)) and other programmed cell deaths like pyroptosis, ferroptosis, necroptosis, each contributing to immunosuppression in distinct ways during the later phases of sepsis. Extensive apoptosis of lymphocytes, such as CD4+, CD8+ T cells, and B cells, is strongly associated with immunosuppression. Apoptosis of dendritic cells further compromises T and B cell survival and can induce T cell anergy or promote regulatory Treg cell proliferation. Moreover, delayed apoptosis and impaired neutrophil function contribute to nosocomial infections and immune dysfunction in sepsis. Interestingly, aberrant NETosis and the subsequent depletion of mature neutrophils also trigger immunosuppression, and neutrophil pyroptosis can positively regulate NETosis. The interaction between programmed cell death 1 (PD-1) or programmed cell death 1 ligand (PD-L1) plays a key role in T cell modulation and neutrophil apoptosis in sepsis. The dendritic cell growth factor, Fms-like tyrosine kinase (FLTEL), increases DC numbers, enhances CD 28 expression, attenuates PD-L1, and improves survival in sepsis. Recently, immunoadjuvant therapies have attracted attention for their potential to restore host physiological immunity and homeostasis in patients with sepsis. This review focuses on several potential immunotherapeutic agents designed to bolster suppressed innate and adaptive immune responses in the management of sepsis.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493214/fullapoptosisautophagyNETosispyroptosisferroptosisnecroptosis cell death |
| spellingShingle | Md. Monirul Islam Md. Monirul Islam Eizo Watanabe Umme Salma Masayuki Ozaki Takayuki Irahara Subaru Tanabe Ryusuke Katsuki Dai Oishi Naoshi Takeyama Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions Frontiers in Immunology apoptosis autophagy NETosis pyroptosis ferroptosis necroptosis cell death |
| title | Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions |
| title_full | Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions |
| title_fullStr | Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions |
| title_full_unstemmed | Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions |
| title_short | Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions |
| title_sort | immunoadjuvant therapy in the regulation of cell death in sepsis recent advances and future directions |
| topic | apoptosis autophagy NETosis pyroptosis ferroptosis necroptosis cell death |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493214/full |
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