Myeloid-Derived Suppressor Cells in Sepsis

Lai, Dengming; Qin, Chaojin; Shu, Qiang

doi:10.1155/2014/598654

Cited by 25 publications

(30 citation statements)

References 67 publications

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“…Thus, early activation of MDSCs during sepsis can be protective but at late stages may lead to the stage of immunoparalysis that proves detrimental to host. Thus, the exact role of MDSCs in sepsis as a friend or foe is still a topic of debate [243][244][245]. However, activation of MDSCs via TLR3, TLR7, TLR8 and TLR9 ligands (i.e.…”

Section: Myeloid-derived Suppressor Cells (Mdscs) In Inflammatory Dismentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

503

346

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The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.

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Section: Myeloid-derived Suppressor Cells (Mdscs) In Inflammatory Dismentioning

confidence: 99%

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Kumar

2018

International Immunopharmacology

503

346

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“…Resuscitation with HTS could induce dramatic early migration and redistribution of MDSCs from bone marrow to peripheral circulation, compared to resuscitation with NS or HES (Lu et al, 2013). The two major subpopulations G-MDSC and M-MDSC have different immunosuppressive mechanisms (Lai et al, 2014;O'Connor et al, 2015;Ost et al, 2016). Normally, G-MDSCs could differentiate into neutrophile granulocyte, while M-MDSC could differentiate into monocyte.…”

Section: Fig 3 Variations Of Mdscs and M-mdsc/g-mdsc Ratio In Mice Bmentioning

confidence: 99%

“…Other studies had also verified the inhibitory function of MDSCs in several chronic infections and autoimmune diseases (Makarenkova et al, 2006). Nevertheless, recent studies even suggested that the expansion of MDSCs in some acute inflammatory processes, such as burns and sepsis, could enhance immune surveillance and innate immune responses, which might be helpful in infection control (Brudecki et al, 2012;Lai et al, 2014;Ost et al, 2016). Additionally, it also implied that MDSCs have divergent gene expression profiles and functions in early and late sepsis.…”

Section: Fig 3 Variations Of Mdscs and M-mdsc/g-mdsc Ratio In Mice Bmentioning

confidence: 99%

“…There has been plenty of research on its role in cancer. Studies also found the variety of the amount, distribution, and function of MDSCs in many other pathological states like infection, trauma, hemorrhagic shock, and sepsis (Brudecki et al, 2012;Janols et al, 2014;Lai et al, 2014;Ost et al, 2016). However, the detailed mechanisms of its regulation and function in those states have not been fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Distribution and differentiation of myeloid-derived suppressor cells after fluid resuscitation in mice with hemorrhagic shock

Jiang

Fang

Ling

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To investigate the distribution and differentiation of myeloid-derived suppressor cells (MDSCs) in hemorrhagic shock mice, which are resuscitated with normal saline (NS), hypertonic saline (HTS), and hydroxyethyl starch (HES). Methods: BALB/c mice were randomly divided into control, NS, HTS, and HES resuscitation groups. Three subgroups (n=8) in each resuscitation group were marked as 2, 24, and 72 h. Flow cytometry was used to detect the MDSCs, monocytic MDSCs (M-MDSCs), and granulocytic/neutrophilic MDSCs (G-MDSCs) in peripheral blood nucleated cells (PBNCs), spleen single-cell suspension, and bone marrow nucleated cells (BMNCs). Results: The MDSCs in BMNCs among three resuscitation groups were lower 2 h after shock, in PBNCs of the HTS group were higher, and in spleen of the NS group were lower (all P<0.05 vs. control). The M-MDSC/G-MDSC ratios in PBNCs of the HTS and HES groups were lower (both P<0.05 vs. control). At 24 h, the MDSCs in PBNCs of the NS and HTS groups were higher, while the spleen MDSCs in the HTS group were higher (all P<0.05 vs. control). The M-MDSC/ G-MDSC ratios were all less in PBNCs, spleen, and BMNCs of the NS and HTS groups, and were lower in BMNCs of the HES group (all P<0.05 vs. control). At 72 h, the elevated MDSCs in PBNCs were presented in the HTS and HES groups, and in spleen the augment turned up in three resuscitation groups (all P<0.05 vs. control). The inclined ratios to M-MDSC were exhibited in spleen of the NS and HTS groups, and in PBNCs of the NS group; the inclination to G-MDSC in BMNCs was shown in the HES group (all P<0.05 vs. control). Conclusions: HTS induces the earlier elevation of MDSCs in peripheral blood and spleen, and influences its distribution and differentiation, while HES has a less effect on the distribution but a stronger impact on the differentiation of MDSCs, especially in bone marrow.

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“…Improvements in patient management and supportive care have drastically improved patient survival through this hyper-inflammatory phase which is subsequently followed by an immunosuppressive phase. Following the cytokine storm, there is a marked decrease in host immunity including apoptosis-induced loss of innate and adaptive immune effector cell populations as well as an increase in immune suppressor cell populations, including T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs) (17)(18)(19)(20). With improvements to patient care, sepsis has transitioned from a hyper-inflammatory disorder to an immunosuppressive disorder, with almost 70% of deaths occurring after the initial inflammatory phase due to the subsequent impaired immunity that make patients more vulnerable to infection recurrence or nosocomial infections (21).…”

Section: Introductionmentioning

confidence: 99%

Development of Systemic Immune Dysregulation in a Rat Trauma Model with Biomaterial-Associated Infection

Vantucci

Ahn

Schenker

et al. 2020

Preprint

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Orthopedic biomaterial-associated infections remain a large clinical challenge, particularly with open fractures and segmental bone loss. Invasion and colonization of bacteria within immuneprivileged canalicular networks of the bone can lead to local, indolent infections that can persist for years without symptoms before eventual catastrophic hardware failure. Host immunity is essential for bacterial clearance and an appropriate healing response, and recent evidence has suggested an association between orthopedic trauma and systemic immune dysregulation and immunosuppression. However, the impact of a local infection on this systemic immune response and subsequent effects on the local response is poorly understood and has not been a major focus for addressing orthopedic injuries and infections. Therefore, this study utilized a model of orthopedic biomaterial-associated infection to investigate the effects of infection on the longterm immune response. Here, despite persistence of a local, indolent infection lacking outward symptoms, there was still evidence of long-term immune dysregulation with systemic increases in MDSCs and decreases in T cells compared to non-infected trauma. Further, the trauma only group exhibited a regulated and coordinated systemic cytokine response, which was not present in the infected trauma group. Locally, the infection group had attenuated macrophage infiltration in the local soft tissue compared to the non-infected group. Our results demonstrate widespread impacts of a localized orthopedic infection on the systemic and local immune responses.Characterization of the immune response to orthopedic biomaterial-associated infection may identify key targets for immunotherapies that could optimize both regenerative and antibiotic interventions, ultimately improving outcomes for these patients.

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Myeloid-Derived Suppressor Cells in Sepsis

Cited by 25 publications

References 67 publications

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

Distribution and differentiation of myeloid-derived suppressor cells after fluid resuscitation in mice with hemorrhagic shock

Development of Systemic Immune Dysregulation in a Rat Trauma Model with Biomaterial-Associated Infection

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