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Review
. 2014:2014:598654.
doi: 10.1155/2014/598654. Epub 2014 Jun 3.

Myeloid-derived suppressor cells in sepsis

Dengming Lai  1 , Chaojin Qin  1 , Qiang Shu  1
Affiliations
Review

Myeloid-derived suppressor cells in sepsis

Dengming Lai et al. Biomed Res Int. 2014.

Abstract

Sepsis is a systemic, deleterious host response to widespread infection. Patients with sepsis will have documented or suspected infection which can progress to a state of septic shock or acute organ dysfunction. Since sepsis is responsible for nearly 3 million cases per year in China and severe sepsis is a common, expensive fatal condition in America, developing new therapies becomes a significant and worthwhile challenge. Clinical research has shown that sepsis-associated immunosuppression plays a central role in patient mortality, and targeted immune-enhancing therapy may be an effective treatment approach in these patients. As part of the inflammatory response during sepsis, there are elevations in the number of myeloid-derived suppressor cells (MDSCs). MDSCs are a heterogeneous population of immature myeloid cells that possess immunosuppressive activities via suppressing T-cell proliferation and activation. The role of MDSCs in sepsis remains uncertain. Some believe activated MDSCs are beneficial to the sepsis host by increasing innate immune responses and antimicrobial activities, while others think expansion of MDSCs leads to adaptive immune suppression and secondary infection. Herein, we discuss the complex role of MDSCs in immune regulation during sepsis, as well as the potential to target these cells for therapeutic benefit.

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Figures

Figure 1
Figure 1
The origin and signaling pathways involved in MDSCs in sepsis. Haematopoietic stem cells (HSCs) differentiate into immature myeloid cells (IMCs) and then quickly differentiate into mature granulocytes, macrophages, or dendritic cells (DCs). In septic conditions, inflammatory factors such as IL-6, IL-10, IL-12, G-CSF, ds RNA, VEGF, and GM-CSF are elevated. They prevent IMCs from differentiating into mature myeloid cells. MDSCs expansion and activation is regulated by many signaling pathways, such as a toll-like receptor (TLR) mediated myeloid differentiation primary response gene 88 (MyD88) signaling and the granulocyte-colony stimulating factor receptor (G-CSFR) mediated the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. They contribute to the increased production of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), and arginase 1 (ARG1). MDSCs in sepsis can reduce the capacity of septic monocytes, macrophages, and neutrophils to respond to bacterial toxins, inhibit the activation of T-cells, and promote Th2 polarization. In addition, MDSCs can secrete several cytokines and chemokines, such as interleukin 10, TNF-α, RANTES, and MIP-1β.
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