Myeloid-Derived Suppressor Cells in Infection: A General Overview

Medina, Eva; Hartl, Dominik

doi:10.1159/000489830

Cited by 94 publications

(101 citation statements)

References 43 publications

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“…Instead, during histotropic phase of infection, we saw increased numbers of CD11b+Gr‐1+ cells in peritoneal fluid. Peritoneal cavity was shown to be an important trafficking site for intestinal immunity; therefore, parasite‐induced cells could migrate through the peritoneum to other lymphoid organs later during infection. Additionally, in our study, low count of MDSC‐like cells in local lymph nodes at 6th dpi coincided with an increased pool of the cells in the blood and the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Role of l‐arginine and CD11b+Gr‐1+ cells in immunosuppression induced by Heligmosomoides polygyrus bakeri

Brodaczewska

Donskow‐Łysoniewska

Krawczak

et al. 2020

Parasite Immunology

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Myeloid‐derived suppressor cells (MDSCs) are heterogeneous population of monocyte and granulocyte progenitors that are highly suppressive against T cells. In BALB/c mice infected with a nematode Heligmosomoides polygyrus bakeri, we studied the dynamics of MDSCs, identified as CD11b+Gr‐1+, induction in different tissues along with the development of parasite infection. We observed that MDSC‐like cells are induced both by larvae and adult stages of H polygyrus bakeri. Gr‐1+ cells of suppressive phenotype are recruited in the bone marrow, peripheral blood and peritoneal cavity during histotropic phase of infection and are present at that time in the intestine wall, where worms reside. Later, during intestinal phase, suppressive Gr‐1+ cells increased in mesenteric lymph nodes and the spleen. l‐arginine metabolism was important for the protective immunity, and parasite‐induced Gr‐1+ cells showed elevated arginase‐1 and iNOS expression. Inhibition of arginase‐1 and l‐arginine administration caused reduced level of infection that coincided with weaker suppressive phenotype of Gr‐1+ cells. We identified that l‐arginine pathway activation and induction of MDSC‐like cells characterize immunosuppressive state during H polygyrus bakeri infection in mice. Our findings confirm the role of MDSCs in parasitic infections and point l‐arginine pathway as a potential target for immunomodulation during nematode infections.

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Section: Discussionmentioning

confidence: 99%

Role of l‐arginine and CD11b+Gr‐1+ cells in immunosuppression induced by Heligmosomoides polygyrus bakeri

Brodaczewska

Donskow‐Łysoniewska

Krawczak

et al. 2020

Parasite Immunology

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“…110,111 On the other hand, we have recently shown that CMV infection in a murine model indeed impairs MDSC differentiation, thereby breaking transplantation tolerance mediated by MDSCs. 113 Furthermore, patients with chronic lung allograft dysfunction also has a lower level of G-MDSCs in the periphery. 112 In support of our findings, in an independent clinical study of lung transplant recipients, G-MDSCs are found to decrease in number with infection while expand in stable lung recipients.…”

Section: Myeloid Derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

“…112 Acute CMV infection is found to inhibit G-MDSC expansion and impair the suppressive function of M-MDSCs. 113 However, there are also conflicting data reporting significant and persistent increase of M-MDSCs after bacterial infection in renal transplant recipients which contributes to postinfection immunodeficiency in these patients. 113 Furthermore, patients with chronic lung allograft dysfunction also has a lower level of G-MDSCs in the periphery.…”

Section: Myeloid Derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

“…112 In support of our findings, in an independent clinical study of lung transplant recipients, G-MDSCs are found to decrease in number with infection while expand in stable lung recipients. 113 Furthermore, patients with chronic lung allograft dysfunction also has a lower level of G-MDSCs in the periphery. 113 However, there are also conflicting data reporting significant and persistent increase of M-MDSCs after bacterial infection in renal transplant recipients which contributes to postinfection immunodeficiency in these patients.…”

Section: Myeloid Derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

“…113 Furthermore, patients with chronic lung allograft dysfunction also has a lower level of G-MDSCs in the periphery. 113 However, there are also conflicting data reporting significant and persistent increase of M-MDSCs after bacterial infection in renal transplant recipients which contributes to postinfection immunodeficiency in these patients. 114 Therefore, it is conceivable that the ultimate impact of infections on MDSCs in the setting of transplantation is determined by numerous variables including the type of pathogens and infections, immunosuppressive regimens and tolerance induction strategies used, and possibly the organ transplanted.…”

Section: Myeloid Derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

See 2 more Smart Citations

Impact of infection on transplantation tolerance

Luo

2019

Immunological Reviews

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Allograft tolerance is the ultimate goal of organ transplantation. Current strategies for tolerance induction mainly focus on inhibiting alloreactive T cells while promoting regulatory immune cells. Pathogenic infections may have direct impact on both effector and regulatory cell populations, therefore can alter host susceptibility to transplantation tolerance induction as well as impair the quality and stability of tolerance once induced. In this review, we will discuss existing data demonstrating the effect of infections on transplantation tolerance, with particular emphasis on the role of the stage of infection (acute, chronic, or latent) and the stage of tolerance (induction or maintenance) in this infection‐tolerance interaction. While the deleterious effect of acute infection on tolerance is mainly driven by proinflammatory cytokines induced shortly after the infection, chronic infection may generate exhausted T cells that could in fact facilitate transplantation tolerance. In addition to pathogenic infections, commensal intestinal microbiota also has numerous significant immunomodulatory effects that can shape the host alloimmunity following transplantation. A comprehensive understanding of these mechanisms is crucial for the development of therapeutic strategies for robustly inducing and stably maintaining transplantation tolerance while preserving host anti‐pathogen immunity in clinically relevant scenarios.

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CXCL16/CXCR6/TGF‐β Feedback Loop Between M‐MDSCs and Treg Inhibits Anti‐Bacterial Immunity During Biofilm Infection

Wu,

Pan,

Chu

et al. 2024

Advanced Science

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Staphylococcus aureus (S. aureus) is a leading cause of Periprosthetic joint infection (PJI), a severe complication after joint arthroplasty. Immunosuppression is a major factor contributing to the infection chronicity of S. aureus PJI, posing significant treatment challenges. This study investigates the relationship between the immunosuppressive biofilm milieu and S. aureus PJI outcomes in both discovery and validation cohorts. This scRNA‐seq analysis of synovium from PJI patients reveals an expansion and heightened activity of monocyte‐related myeloid‐derived suppressor cells (M‐MDSCs) and regulatory T cells (Treg). Importantly, CXCL16 is significantly upregulated in M‐MDSCs, with its corresponding CXCR6 receptor also elevated on Treg. M‐MDSCs recruit Treg and enhance its activity via CXCL16‐CXCR6 interactions, while Treg secretes TGF‐β, inducing M‐MDSCs proliferation and immunosuppressive activity. Interfering with this cross‐talk in vivo using Treg‐specific CXCR6 knockout PJI mouse model reduces M‐MDSCs/Treg‐mediated immunosuppression and alleviates bacterial burden. Immunohistochemistry and recurrence analysis show that PJI patients with CXCR6high synovium have poor prognosis. This findings highlight the critical role of CXCR6 in Treg in orchestrating an immunosuppressive microenvironment and biofilm persistence during PJI, offering potential targets for therapeutic intervention.

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Myeloid-Derived Suppressor Cells in Infection: A General Overview

Cited by 94 publications

References 43 publications

Role of l‐arginine and CD11b+Gr‐1+ cells in immunosuppression induced by Heligmosomoides polygyrus bakeri

Role of l‐arginine and CD11b+Gr‐1+ cells in immunosuppression induced by Heligmosomoides polygyrus bakeri

Impact of infection on transplantation tolerance

CXCL16/CXCR6/TGF‐β Feedback Loop Between M‐MDSCs and Treg Inhibits Anti‐Bacterial Immunity During Biofilm Infection

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