Granulocytic Myeloid Derived Suppressor Cells Expansion during Active Pulmonary Tuberculosis Is Associated with High Nitric Oxide Plasma Level

Daker, Sary El; Sacchi, Alessandra; Tempestilli, Massimo; Carducci, Claudia; Goletti, Delia; Vanini, Valentina; Colizzi, Vittorio; Lauria, F.; Martini, Federico; Martino, Angelo

doi:10.1371/journal.pone.0123772

Cited by 66 publications

(89 citation statements)

References 21 publications

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“…The study found a strong correlation between the accumulation of MDSCs and lethality of disease and suggested that host‐directed therapies targeting depletion of MDSCs could provide a vital breakthrough in ameliorating the disease. These findings were corroborated in humans, where increased expansion of MDSCs in bronchoalveolar lavage, as well as in peripheral blood, of pulmonary TB patients was observed as compared to healthy donors . However, one key question that remains is what controls the expansion of MDSCs in TB‐susceptible and TB‐resistant humans, and how?…”

Section: Macrophage Heterogeneity and M Tuberculosis Infectionmentioning

confidence: 63%

“…Infected monocytes/macrophages can reach the bone marrow and interact with hematopoietic stem cells (HSCs) and educate them for generating epigenetically modified macrophages that are much more competent in innate immune response than naive macrophages . Myeloid‐derived suppressor cells (MDSCs) can also be recruited at the site of infection and can negatively influence infection control by inhibiting macrophage and T cell responses via the cytokines and chemokines they produce …”

Section: Macrophage Heterogeneity and M Tuberculosis Infectionmentioning

confidence: 99%

“…61,62 Myeloid-derived suppressor cells (MDSCs) can also be recruited at the site of infection and can negatively influence infection control by inhibiting macrophage and T cell responses via the cytokines and chemokines they produce. [63][64][65]68 The role of AMs in the dissemination of M. tuberculosis from alveoli to lung interstitium has recently been demonstrated in a murine TB model. 42 After localization of M. tuberculosis infected AMs to lung interstitium, monocyte-derived macrophages take up the bacilli in a process involving IL-1 receptor mediated signaling between these two subsets of macrophages.…”

Section: Macrophage Heterogeneity and M Tuberculosis Infectionmentioning

confidence: 99%

See 2 more Smart Citations

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: Macrophage Heterogeneity and M Tuberculosis Infectionmentioning

confidence: 63%

Section: Macrophage Heterogeneity and M Tuberculosis Infectionmentioning

confidence: 99%

Section: Macrophage Heterogeneity and M Tuberculosis Infectionmentioning

confidence: 99%

See 1 more Smart Citation

Macrophage heterogeneity and plasticity in tuberculosis

Khan

Singh

Hunter

et al. 2019

Journal of Leukocyte Biology

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“…136 Mesenchymal stromal cells (MSC) are nonhematopoietic progenitor cells with immunomodulatory and antibacterial properties, [137][138] that improve immune responses and lung pathology in human and murine TB. [139][140] Another immunotherapeutic approach involves modulation of immune regulatory cells, specifically myeloid-derived suppressor cells (MDSC) [141][142] MDSC are increased in TB, display T-cell immunosuppressive properties, [143][144][145] and harbour Mtb, suggesting that MDSC-targeting strategies should also be considered in TB HDT design. The promise of use T-cell therapy, with or without T-cell receptor (TCR) manipulations to increase affinity for antigen has shown promise for CMV treatment, and could be beneficial in TB.…”

Section: Cellular Therapymentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

308

275

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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“…This is in part due to the host‐derived immune suppressive cells such as myeloid‐derived suppressor cells (MDSCs). The accumulation of MDSCs hinders protective immune responses to cancer and infectious diseases such as tuberculosis, AIDS, hepatitis C, hepatitis B, pneumonia, and Staphylococcus aurous infection . Importantly, an elevation of MDSCs is associated with a reduced efficacy of vaccines .…”

Section: Introductionmentioning

confidence: 99%

Gr1−/lowCD11b−/lowMHCII+ myeloid cells boost T cell anti-tumor efficacy

Payne

Aqbi

Butler

et al. 2018

Journal of Leukocyte Biology

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Conventional APCs that express MHC class II (MHCII) and co-stimulatory molecules include dendritic cells (DCs) and macrophages. Beyond these conventional APCs, immune stimulatory cells have been more recently shown to extend to a class of atypical APCs, composed of mast cells, basophils, and eosinophils. Here, we describe a unique type of APC, Gr1 CD11b cells with a granularity and size characteristic of myeloid cells and with the ability to present Ag for crosspresentation. These cells constitutively express MHCII and the costimulatory molecules, CD80, CD86, and CD40. They do not express pan markers of myeloid DCs (CD11c), plasmacytoid DCs (Ly6C), or macrophages (F4/80), and their frequency is inversely correlated with myeloid-derived suppressor cells (MDSCs) in tumor-bearing mice. Among splenocytes, they are more abundant than DCs and macrophages, and they exhibit antitumor immune stimulatory function at a steady state without further activation, ex vivo. They are also found within the tumor bed where they retain their immune stimulatory function. Our findings suggest the use of these novel APCs in additional preclinical studies to further investigate their utility in APC-based cancer immunotherapies.

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Granulocytic Myeloid Derived Suppressor Cells Expansion during Active Pulmonary Tuberculosis Is Associated with High Nitric Oxide Plasma Level

Cited by 66 publications

References 21 publications

Macrophage heterogeneity and plasticity in tuberculosis

Macrophage heterogeneity and plasticity in tuberculosis

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Gr1−/lowCD11b−/lowMHCII+ myeloid cells boost T cell anti-tumor efficacy

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