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

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that suppress immune responses, originally identified in cancer patients.
• MDSCs are increasingly recognized in various conditions, including chronic inflammation, autoimmunity, and bacterial infections like sepsis.
• Human MDSCs are broadly classified into monocytic (Mo-MDSCs) and granulocytic (PMN-MDSCs) subtypes, with their representation in non-cancer diseases still under investigation.

Purpose of the Study:

• To investigate the presence and characteristics of MDSCs in sepsis patients, comparing total peripheral blood with density gradient-centrifuged blood.
• To determine if the causative microorganisms in sepsis influence the type and frequency of MDSC populations.
• To characterize a specific PMN-MDSC-like population found in sepsis, including its functional and phenotypic properties.

Main Methods:

• Analysis of potential MDSCs in sepsis patients' total peripheral blood and density gradient-centrifuged blood.
• Flow cytometry to identify and quantify Mo-MDSCs and PMN-MDSCs based on cell surface markers (e.g., CD14, HLA-DR).
• In vitro functional assays to assess T cell proliferation suppression by MDSC variants, including analysis of reactive oxygen species (ROS) production and cytokine profiles (IL-10, TNF-α).

Main Results:

• All sepsis patients exhibited a high frequency of typical CD14(+)HLA-DR(low) Mo-MDSCs.
• Typical PMN-MDSCs and a distinct CD14(low) PMN-MDSC-like population were preferentially observed in gram-positive sepsis.
• The CD14(low) PMN-MDSC variant suppressed T cell proliferation via ROS, showed an elevated IL-10:TNF-α ratio, and displayed immature characteristics (blast morphology, low cytokine levels).

Conclusions:

• Sepsis is associated with an enrichment of cells exhibiting MDSC features, forming a spectrum of suppressive myeloid cells.
• The microbial origin of sepsis significantly impacts the MDSC profile, leading to substantial interindividual patient variation.
• The identification of immature, immunosuppressive PMN-MDSC-like cells in gram-positive sepsis highlights the need for further research into their specific role and therapeutic targeting.