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A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases.

Janols, Helena LU ; Bergenfelz, Caroline LU ; Allaoui, Roni LU ; Larsson, Anna-Karin A LU ; Rydén, Lisa LU ; Björnsson, Sven LU ; Janciauskiene, Sabina LU ; Wullt, Marlene LU ; Bredberg, Anders LU and Leandersson, Karin LU (2014) In Journal of Leukocyte Biology 96(5). p.685-693
Abstract
The causative microorganisms dictate the type of MDSC generated in sepsis patients, and a large proportion of PMN-MDSCs in gram-positive sepsis includes immunosuppressive myeloid blasts. MDSCs constitute a heterogeneous population of immature myeloid cells that potently suppress immune responses. They were identified originally in cancer patients and have since been reported to occur also in chronic inflammation, autoimmunity, and even bacterial infections. Human MDSCs are commonly divided into Mo-MDSCs and granulocytic (PMN-MDSCs) subtypes. To what extent the bona fide cancer MDSCs are representative of the proposed MDSCs found in other diseases is not well known. PMN-MDSCs have been found previously to be enriched among LDGs in density... (More)
The causative microorganisms dictate the type of MDSC generated in sepsis patients, and a large proportion of PMN-MDSCs in gram-positive sepsis includes immunosuppressive myeloid blasts. MDSCs constitute a heterogeneous population of immature myeloid cells that potently suppress immune responses. They were identified originally in cancer patients and have since been reported to occur also in chronic inflammation, autoimmunity, and even bacterial infections. Human MDSCs are commonly divided into Mo-MDSCs and granulocytic (PMN-MDSCs) subtypes. To what extent the bona fide cancer MDSCs are representative of the proposed MDSCs found in other diseases is not well known. PMN-MDSCs have been found previously to be enriched among LDGs in density gradient-centrifuged blood. In this study, we analyzed potential MDSCs in sepsis patients with different causative microorganisms, using total peripheral blood compared with density gradient-centrifuged blood. We found a high frequency of typical CD14(+)HLA-DR(low) Mo-MDSCs in all sepsis patients, whereas the typical PMN-MDSCs, as well as a prominent CD14(low) PMN-MDSC-like population, appeared preferentially in gram-positive cases. The CD14(low) PMN-MDSC variant was demonstrated to suppress T cell proliferation in vitro via a ROS-dependent mechanism, to display an increased IL-10:TNF-α ratio, and to present with signs of immaturity: blast morphology and low cytokine levels. We conclude that a spectrum of cells with MDSC features is enriched in sepsis and that the microbial origin of sepsis contributes to the substantial interindividual patient variation in the MDSC pattern. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Leukocyte Biology
volume
96
issue
5
pages
685 - 693
publisher
Society for Leukocyte Biology
external identifiers
  • pmid:24929004
  • wos:000344759800005
  • scopus:84908289124
ISSN
1938-3673
DOI
10.1189/jlb.5HI0214-074R
language
English
LU publication?
yes
id
5b06f59b-38d5-4902-a996-afcf9ca22938 (old id 4528481)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24929004?dopt=Abstract
date added to LUP
2014-07-05 21:37:58
date last changed
2017-11-19 03:05:02
@article{5b06f59b-38d5-4902-a996-afcf9ca22938,
  abstract     = {The causative microorganisms dictate the type of MDSC generated in sepsis patients, and a large proportion of PMN-MDSCs in gram-positive sepsis includes immunosuppressive myeloid blasts. MDSCs constitute a heterogeneous population of immature myeloid cells that potently suppress immune responses. They were identified originally in cancer patients and have since been reported to occur also in chronic inflammation, autoimmunity, and even bacterial infections. Human MDSCs are commonly divided into Mo-MDSCs and granulocytic (PMN-MDSCs) subtypes. To what extent the bona fide cancer MDSCs are representative of the proposed MDSCs found in other diseases is not well known. PMN-MDSCs have been found previously to be enriched among LDGs in density gradient-centrifuged blood. In this study, we analyzed potential MDSCs in sepsis patients with different causative microorganisms, using total peripheral blood compared with density gradient-centrifuged blood. We found a high frequency of typical CD14(+)HLA-DR(low) Mo-MDSCs in all sepsis patients, whereas the typical PMN-MDSCs, as well as a prominent CD14(low) PMN-MDSC-like population, appeared preferentially in gram-positive cases. The CD14(low) PMN-MDSC variant was demonstrated to suppress T cell proliferation in vitro via a ROS-dependent mechanism, to display an increased IL-10:TNF-α ratio, and to present with signs of immaturity: blast morphology and low cytokine levels. We conclude that a spectrum of cells with MDSC features is enriched in sepsis and that the microbial origin of sepsis contributes to the substantial interindividual patient variation in the MDSC pattern.},
  author       = {Janols, Helena and Bergenfelz, Caroline and Allaoui, Roni and Larsson, Anna-Karin A and Rydén, Lisa and Björnsson, Sven and Janciauskiene, Sabina and Wullt, Marlene and Bredberg, Anders and Leandersson, Karin},
  issn         = {1938-3673},
  language     = {eng},
  number       = {5},
  pages        = {685--693},
  publisher    = {Society for Leukocyte Biology},
  series       = {Journal of Leukocyte Biology},
  title        = {A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases.},
  url          = {http://dx.doi.org/10.1189/jlb.5HI0214-074R},
  volume       = {96},
  year         = {2014},
}