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Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis

Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the...

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Autores principales: Ruan, Wei-Shuyi, Feng, Meng-Xiao, Xu, Jia, Xu, Ying-Ge, Song, Cong-Ying, Lin, Li-Ying, Li, Li, Lu, Yuan-Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347749/
https://www.ncbi.nlm.nih.gov/pubmed/32719675
http://dx.doi.org/10.3389/fimmu.2020.01299
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author Ruan, Wei-Shuyi
Feng, Meng-Xiao
Xu, Jia
Xu, Ying-Ge
Song, Cong-Ying
Lin, Li-Ying
Li, Li
Lu, Yuan-Qiang
author_facet Ruan, Wei-Shuyi
Feng, Meng-Xiao
Xu, Jia
Xu, Ying-Ge
Song, Cong-Ying
Lin, Li-Ying
Li, Li
Lu, Yuan-Qiang
author_sort Ruan, Wei-Shuyi
collection PubMed
description Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis.
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spelling pubmed-73477492020-07-26 Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis Ruan, Wei-Shuyi Feng, Meng-Xiao Xu, Jia Xu, Ying-Ge Song, Cong-Ying Lin, Li-Ying Li, Li Lu, Yuan-Qiang Front Immunol Immunology Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis. Frontiers Media S.A. 2020-07-03 /pmc/articles/PMC7347749/ /pubmed/32719675 http://dx.doi.org/10.3389/fimmu.2020.01299 Text en Copyright © 2020 Ruan, Feng, Xu, Xu, Song, Lin, Li and Lu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ruan, Wei-Shuyi
Feng, Meng-Xiao
Xu, Jia
Xu, Ying-Ge
Song, Cong-Ying
Lin, Li-Ying
Li, Li
Lu, Yuan-Qiang
Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis
title Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis
title_full Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis
title_fullStr Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis
title_full_unstemmed Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis
title_short Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis
title_sort early activation of myeloid-derived suppressor cells participate in sepsis-induced immune suppression via pd-l1/pd-1 axis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347749/
https://www.ncbi.nlm.nih.gov/pubmed/32719675
http://dx.doi.org/10.3389/fimmu.2020.01299
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