title: A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in gram-positive cases.
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.
authors.affiliation: Departments of Infectious Diseases, Center for Molecular Pathology, and.
authors.forename: Helena
authors.initials: H
authors.lastname: Janols
authors.affiliation: Center for Molecular Pathology, and.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bergenfelz
authors.affiliation: Center for Molecular Pathology, and.
authors.forename: Roni
authors.initials: R
authors.lastname: Allaoui
authors.affiliation: Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, Malmo, Sweden; and.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Larsson
authors.affiliation: Surgery, and.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Cytometry Laboratory and Department of Laboratory Medicine, Skane University Hospital, and.
authors.forename: Sven
authors.initials: S
authors.lastname: Björnsson
authors.affiliation: Department of Pulmonology, Hannover Medical School, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.affiliation: Departments of Infectious Diseases.
authors.forename: Marlene
authors.initials: M
authors.lastname: Wullt
authors.affiliation: Medical Microbiology.
authors.forename: Anders
authors.initials: A
authors.lastname: Bredberg
authors.affiliation: Center for Molecular Pathology, and karin.leandersson@med.lu.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Leandersson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D016207:Cytokines
keywords: CD11c; CD14; Ficoll; MDSC; cancer; granulocyte