Monocytic Myeloid-Derived Suppressor Cells in Chronic Infections

Dorhoi, Anca; Plessis, Nelita du

doi:10.3389/fimmu.2017.01895

Cited by 123 publications

(137 citation statements)

References 170 publications

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“…Myeloid‐derived suppressor cells (MDSCs) are another population of macrophages that originate from myeloid progenitors . While MDSCs are known to remain arrested in an immature state of macrophage differentiation, accumulating evidence clearly demonstrates their role in suppression of T‐cell responses during infection . In addition to their direct suppressive effects on adaptive immune responses, MDSCs can also affect other subsets of macrophages by modulating their cytokine production …”

Section: The Diversity Of Macrophages and Their Functionsmentioning

confidence: 99%

“…MDSCs are known to remain arrested in an immature state of macrophage differentiation, accumulating evidence clearly demonstrates their role in suppression of T-cell responses during infection. 28 In addition to their direct suppressive effects on adaptive immune responses, MDSCs can also affect other subsets of macrophages by modulating their cytokine production. 29 In recent years, it has become evident that cytokines and chemokines produced by immune and nonimmune cells in bone marrow can also induce heterogeneity in macrophage populations via activation of hematopoietic stem cells (HSCs).…”

Section: Whilementioning

confidence: 99%

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Macrophage heterogeneity and plasticity in tuberculosis

Khan

Singh

Hunter

et al. 2019

Journal of Leukocyte Biology

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Macrophages are the primary host cells for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), during its intracellular survival in humans. The pathogen has a remarkable capacity to survive within the hostile environment of macrophages. However, primary infection does not result in active TB disease in most individuals. The majority of individuals remain latently infected, wherein the bacteria are held in check by the host immune response. Nevertheless, such individuals can develop active TB later upon the decline in their immune status. In contrast, in a small fraction of infected individuals, the host immune response fails to control the growth of M. tuberculosis bacilli, and granulomatous TB develops progressively. Elucidating the molecular and phenotypic events that govern the outcome of the infection within macrophages is fundamental to understanding the key features of these cells that could be equally critical in infection control. The molecular details of the M. tuberculosis‐macrophage interaction continue to be discerned, and emerging evidence suggests that macrophage population that participate in infection is heterogeneous. While the local environment and developmental origin could influence the phenotypic heterogeneity and functional plasticity of macrophages, M. tuberculosis has also been demonstrated to modulate the polarization of macrophages. In this review, we draw on work investigating specialized macrophage populations and their interactions with M. tuberculosis with respect to pathogenesis and specific immune responses. Understanding the mechanisms that control the repertoire of macrophage phenotypes and behaviors during infection may provide prospects for novel TB control strategies through modulation of immunobiological functions of macrophages.

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Section: The Diversity Of Macrophages and Their Functionsmentioning

confidence: 99%

Section: Whilementioning

confidence: 99%

Macrophage heterogeneity and plasticity in tuberculosis

Khan

Singh

Hunter

et al. 2019

Journal of Leukocyte Biology

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“…Treg-depletion has only a minor effect, whereas T-cell proliferation remains inhibited despite the absence of B220 + and CD11c + cells 7 . Nevertheless, T-cell suppression in chronically infected mice has been associated with the expansion of monocytic-like (CD11b + Ly6C + Ly6G low phenotype), neutrophilic-like (CD11b + Ly6C low Ly6G + phenotype) and eosonophilic-like (CD11b + Ly6C low Ly6G low phenotype) MDSCs 7;8;9;10;11 , affirming the dominant immunosuppressive role of MDSCs during chronic S. aureus infections.…”

mentioning

confidence: 90%

ChronicStaphylococcus aureusinfection is cured by theory-driven therapy

Zhao

Khailaie

et al. 2020

Preprint

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19Staphylococcus aureus (S. aureus) is a challenging human pathogen due to its ability to evade the 20 immune system and resist multidrug antibiotics. These evasive strategies lead to chronic and re-21 current infections. Many studies have documented that during chronic infections Myeloid Derived 22 Suppressor Cells (MDSCs) exert immunosuppressive mechanisms on T cells. A mathematical 23 model explains how the steady state of chronic infection can be disturbed and suggests therapeutic 24 strategies to clear the infection. Model-driven suggestions were tested experimentally and con-25 firmed complete clearance of S. aureus chronic infection. 26 Keywords 27 Myeloid Derived Suppressor Cells, MDSCs, Staphylococcus aureus, chronic infection, mathematical model, 28 therapy, cure, heat-killed cells 29Staphylococcus aureus (S. aureus) is a bacterial human pathogen colonizing 20%-30% of the world pop-30 ulation and responsible for the genesis of nosocomial-acquired and community-acquired bacterial infections. 31 Colonization by S. aureus is typically asymptomatical, implying an equilibrated state between host and bac-32 terium. However, the bacterium can become opportunistic often post-surgery or after implantation of medical 33 devices and can cause skin and soft tissue infections, such as dermatitis, impetigo, and cellulitis 1 , as well as 34 life-threatening conditions like pneumonia and chronic osteomyelitis 2 . Additionally, individuals with immune 35 deficiencies are more susceptible to S. aureus infections. The pathogen constitutes a serious problem in clin-36 ics worldwide because it uses multiple mechanisms to persist in the host. These include strategies of bacterial 37 1 evasion, multi-drug antibiotic resistance, immunosuppression 3 or manipulation of the host's immune regulatory 38 mechanisms, 4;5 which lead to chronic and difficult-to-treat infections. 39Typically, immunosuppression is achieved via regulatory T cells (Tregs), T cell lysis, regulatory B cells 40 (Bregs) 6 , and Myeloid-Derived Suppressor Cells (MDSCs). In the case of S. aureus chronic infections, immuno-41 suppression is not attributed to Bregs, tolerogenic dendritic cells, nor Tregs 7 . Treg-depletion has only a minor 42 effect, whereas T-cell proliferation remains inhibited despite the absence of B220 + and CD11c + cells 7 . Never-43 theless, T-cell suppression in chronically infected mice has been associated with the expansion of monocytic-like 44 (CD11b + Ly6C + Ly6G low phenotype), neutrophilic-like (CD11b + Ly6C low Ly6G + phenotype) and eosonophilic-45 like (CD11b + Ly6C low Ly6G low phenotype) MDSCs 7;8;9;10;11 , affirming the dominant immunosuppressive role of 46 MDSCs during chronic S. aureus infections. 47MDSCs constitute a heterogeneous population of immature myeloid cells, which exert their suppressive 48 effect on T cells by producing reactive oxygen species, nitric oxide, arginase, and inducible nitric oxide syn-49 thase. Significant MDSC expansion and the consequent immunosuppressive effect were reported in long-lasting 50 p...

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“…106 For transplantation tolerance, perioperative recipient infusion of MDSCs has been shown to prolong allograft survival in mouse islet transplantation, 107 corneal transplantation 108 and skin transplantation. 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. On the one hand, both G-MDSCs and M-MDSCs have been shown to expand postinfection, which in turn inhibits subsequent T cell immune responses.…”

Section: Myeloid Derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

“…On the one hand, both G-MDSCs and M-MDSCs have been shown to expand postinfection, which in turn inhibits subsequent T cell immune responses. 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. 112 Acute CMV infection is found to inhibit G-MDSC expansion and impair the suppressive function of M-MDSCs.…”

Section: Myeloid Derived Suppressor Cells (Mdscs)mentioning

confidence: 99%

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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Monocytic Myeloid-Derived Suppressor Cells in Chronic Infections

Cited by 123 publications

References 170 publications

Macrophage heterogeneity and plasticity in tuberculosis

Macrophage heterogeneity and plasticity in tuberculosis

ChronicStaphylococcus aureusinfection is cured by theory-driven therapy

Impact of infection on transplantation tolerance

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