scholarly journals Immunoregulation byTaenia crassicepsand Its Antigens

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Alberto N. Peón ◽  
Arlett Espinoza-Jiménez ◽  
Luis I. Terrazas
Keyword(s):  
Immune Response ◽  
Adult Stage ◽  
Parasitic Infection ◽  
Suppressor Cells ◽  
Infection Model ◽  
Myeloid Derived Suppressor Cells ◽  
Alternatively Activated Macrophages ◽  
Cestode Parasite ◽  
Alternatively Activated ◽  
Strong Capacity

Taenia crassicepsis a cestode parasite of rodents (in its larval stage) and canids (in its adult stage) that can also parasitize immunocompromised humans. We have studied the immune response elicited by this helminth and its antigens in mice and human cells, and have discovered that they have a strong capacity to induce chronic Th2-type responses that are primarily characterized by high levels of Th2 cytokines, low proliferative responses in lymphocytes, an immature and LPS-tolerogenic profile in dendritic cells, the recruitment of myeloid-derived suppressor cells and, specially, alternatively activated macrophages. We also have utilized the immunoregulatory capabilities of this helminth to successfully modulate autoimmune responses and the outcome of other infectious diseases. In the present paper, we review the work of others and ourselves with regard to the immune response induced byT. crassicepsand its antigens, and we compare the advances in our understanding of this parasitic infection model with the knowledge that has been obtained from other selected models.

Monocytic myeloid-derived suppressor cells home to tumor-draining lymph nodes via CCR2 and locally modulate the immune response

2021 ◽  
Vol 362 ◽  
pp. 104296
Author(s):  
Qods Lahmar ◽  
Elio Schouppe ◽  
Yannick Morias ◽  
Eva Van Overmeire ◽  
Patrick De Baetselier ◽  
...  
Keyword(s):  
Immune Response ◽  
Lymph Nodes ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Draining Lymph Nodes

scholarly journals Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19)

2020 ◽  
Vol 27 (11) ◽  
pp. 3196-3207 ◽  
Author(s):  
Chiara Agrati ◽  
Alessandra Sacchi ◽  
Veronica Bordoni ◽  
Eleonora Cimini ◽  
Stefania Notari ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Functions ◽  
Convalescent Phase

Abstract SARS-CoV-2 is associated with a 3.4% mortality rate in patients with severe disease. The pathogenesis of severe cases remains unknown. We performed an in-depth prospective analysis of immune and inflammation markers in two patients with severe COVID-19 disease from presentation to convalescence. Peripheral blood from 18 SARS-CoV-2-infected patients, 9 with severe and 9 with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells (MDSCs) and cytokine profiles. MDSC functionality was tested in vitro. In four severe and in four mild patients, a longitudinal analysis was performed daily from the day of admission to the early convalescent phase. Early after admission severe patients showed neutrophilia, lymphopenia, increase in effector T cells, a persisting higher expression of CD95 on T cells, higher serum concentration of IL-6 and TGF-β, and a cytotoxic profile of NK and T cells compared with mild patients, suggesting a highly engaged immune response. Massive expansion of MDSCs was observed, up to 90% of total circulating mononuclear cells in patients with severe disease, and up to 25% in the patients with mild disease; the frequency decreasing with recovery. MDSCs suppressed T-cell functions, dampening excessive immune response. MDSCs decline at convalescent phase was associated to a reduction in TGF-β and to an increase of inflammatory cytokines in plasma samples. Substantial expansion of suppressor cells is seen in patients with severe COVID-19. Further studies are required to define their roles in reducing the excessive activation/inflammation, protection, influencing disease progression, potential to serve as biomarkers of disease severity, and new targets for immune and host-directed therapeutic approaches.

scholarly journals Calcium/Calmodulin Dependent Protein Kinase Kinase 2 Regulates the Expansion of Tumor-Induced Myeloid-Derived Suppressor Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Huang ◽  
Yaping Liu ◽  
Anthony Luz ◽  
Mark Berrong ◽  
Joel N. Meyer ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Kinase ◽  
Bone Marrow Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
T Cell Response ◽  
Tumor Rejection ◽  
Myeloid Derived Suppressor Cells ◽  
Calcium Calmodulin Dependent

Myeloid-derived suppressor cells (MDSCs) are a hetero geneous group of cells, which can suppress the immune response, promote tumor progression and impair the efficacy of immunotherapies. Consequently, the pharmacological targeting of MDSC is emerging as a new immunotherapeutic strategy to stimulate the natural anti-tumor immune response and potentiate the efficacy of immunotherapies. Herein, we leveraged genetically modified models and a small molecule inhibitor to validate Calcium-Calmodulin Kinase Kinase 2 (CaMKK2) as a druggable target to control MDSC accumulation in tumor-bearing mice. The results indicated that deletion of CaMKK2 in the host attenuated the growth of engrafted tumor cells, and this phenomenon was associated with increased antitumor T cell response and decreased accumulation of MDSC. The adoptive transfer of MDSC was sufficient to restore the ability of the tumor to grow in Camkk2-/- mice, confirming the key role of MDSC in the mechanism of tumor rejection. In vitro studies indicated that blocking of CaMKK2 is sufficient to impair the yield of MDSC. Surprisingly, MDSC generated from Camkk2-/- bone marrow cells also showed a higher ability to terminally differentiate toward more immunogenic cell types (e.g inflammatory macrophages and dendritic cells) compared to wild type (WT). Higher intracellular levels of reactive oxygen species (ROS) accumulated in Camkk2-/- MDSC, increasing their susceptibility to apoptosis and promoting their terminal differentiation toward more mature myeloid cells. Mechanistic studies indicated that AMP-activated protein kinase (AMPK), which is a known CaMKK2 proximal target controlling the oxidative stress response, fine-tunes ROS accumulation in MDSC. Accordingly, failure to activate the CaMKK2-AMPK axis can account for the elevated ROS levels in Camkk2-/- MDSC. These results highlight CaMKK2 as an important regulator of the MDSC lifecycle, identifying this kinase as a new druggable target to restrain MDSC expansion and enhance the efficacy of anti-tumor immunotherapy.

scholarly journals Reduced Expression of Autophagy Markers and Expansion of Myeloid-Derived Suppressor Cells Correlate With Poor T Cell Response in Severe COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Sergej Tomić ◽  
Jelena Đokić ◽  
Dejan Stevanović ◽  
Nataša Ilić ◽  
Alisa Gruden-Movsesijan ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Response ◽  
Suppressor Cells ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Myeloid Derived Suppressor Cells ◽  
Immunological Mechanisms

Widespread coronavirus disease (COVID)-19 is causing pneumonia, respiratory and multiorgan failure in susceptible individuals. Dysregulated immune response marks severe COVID-19, but the immunological mechanisms driving COVID-19 pathogenesis are still largely unknown, which is hampering the development of efficient treatments. Here we analyzed ~140 parameters of cellular and humoral immune response in peripheral blood of 41 COVID-19 patients and 16 age/gender-matched healthy donors by flow-cytometry, quantitative PCR, western blot and ELISA, followed by integrated correlation analyses with ~30 common clinical and laboratory parameters. We found that lymphocytopenia in severe COVID-19 patients (n=20) strongly affects T, NK and NKT cells, but not B cells and antibody production. Unlike increased activation of ICOS-1+ CD4+ T cells in mild COVID-19 patients (n=21), T cells in severe patients showed impaired activation, low IFN-γ production and high functional exhaustion, which correlated with significantly down-regulated HLA-DR expression in monocytes, dendritic cells and B cells. The latter phenomenon was followed by lower interferon responsive factor (IRF)-8 and autophagy-related genes expressions, and the expansion of myeloid derived suppressor cells (MDSC). Intriguingly, PD-L1-, ILT-3-, and IDO-1-expressing monocytic MDSC were the dominant producers of IL-6 and IL-10, which correlated with the increased inflammation and accumulation of regulatory B and T cell subsets in severe COVID-19 patients. Overall, down-regulated IRF-8 and autophagy-related genes expression, and the expansion of MDSC subsets could play critical roles in dysregulating T cell response in COVID-19, which could have large implications in diagnostics and design of novel therapeutics for this disease.

scholarly journals Overcoming the Immunosuppressive Tumor Microenvironment in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2018
Author(s):  
Fatih M. Uckun
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Nk Cell ◽  
Suppressor Cells ◽  
Alternatively Activated Macrophages ◽  
Effector T Cell ◽  
Immunosuppressive Tumor Microenvironment ◽  
Cytotoxic Effector ◽  
Alternatively Activated

SeverFigurel cellular elements of the bone marrow (BM) microenvironment in multiple myeloma (MM) patients contribute to the immune evasion, proliferation, and drug resistance of MM cells, including myeloid-derived suppressor cells (MDSCs), tumor-associated M2-like, “alternatively activated” macrophages, CD38+ regulatory B-cells (Bregs), and regulatory T-cells (Tregs). These immunosuppressive elements in bidirectional and multi-directional crosstalk with each other inhibit both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells. Immunomodulatory imide drugs (IMiDs), protease inhibitors (PI), monoclonal antibodies (MoAb), adoptive T-cell/NK cell therapy, and inhibitors of anti-apoptotic signaling pathways have emerged as promising therapeutic platforms that can be employed in various combinations as part of a rationally designed immunomodulatory strategy against an immunosuppressive tumor microenvironment (TME) in MM. These platforms provide the foundation for a new therapeutic paradigm for achieving improved survival of high-risk newly diagnosed as well as relapsed/refractory MM patients. Here we review the scientific rationale and clinical proof of concept for each of these platforms.

scholarly journals Taenia crassiceps Antigens Control Experimental Type 1 Diabetes by Inducing Alternatively Activated Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Arlett Espinoza-Jiménez ◽  
Roberto De Haro ◽  
Luis I. Terrazas
Keyword(s):  
Type 1 Diabetes ◽  
Suppressor Cells ◽  
Activated Macrophages ◽  
Taenia Crassiceps ◽  
Alternatively Activated Macrophages ◽  
Helminth Infections ◽  
Experimental Type ◽  
Classically Activated Macrophages ◽  
Alternatively Activated

Type 1 diabetes (T1D) is an autoimmune disease caused by the selective destruction of the pancreatic β-cells, causing inability to produce insulin. Proinflammatory cytokines such as IL-1β, IL-6, TNF-α, IFN-γ, IL-12, IL-17, and NO can be released by CD4 and CD8+ lymphocytes as well as by classically activated macrophages (CAMϕs), which are important in the development of T1D. Helminth infections have been shown to prevent T1D, mainly through Th2-biased responses and increased recruitment of regulatory cell populations. Previously, we have shown that Taenia crassiceps infection in mice significantly reduces hyperglycemia, insulitis, and the incidence of T1D. In this study, we determined whether T. crassiceps-derived products such as soluble (TcS) or excreted/secreted (TcES) antigens might have a beneficial influence on the development of experimental T1D. Treatment with different doses before or after induction of T1D was analyzed. Mice that were pretreated with TcS were unable to develop T1D, whereas those receiving TcES early after T1D induction displayed significantly reduced insulitis and hyperglycemia along with increased recruitment of alternatively activated macrophages (AAMϕs) and myeloid-derived suppressor cells (MDSCs). Finally, we examined the modulatory role of AAMϕs on T1D by depleting macrophages with clodronate-loaded liposomes, demonstrating that AAMϕs are key cells in T1D regulation.

scholarly journals GMI, an Immunomodulatory Peptide from Ganoderma microsporum, Restrains Periprosthetic Joint Infections via Modulating the Functions of Myeloid-Derived Suppressor Cells and Effector T Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 6854
Author(s):  
Kuo-Ti Peng ◽  
Jiun-Liang Chen ◽  
Liang-Tseng Kuo ◽  
Pei-An Yu ◽  
Wei-Hsiu Hsu ◽  
...  
Keyword(s):  
T Cells ◽  
Bacterial Infections ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Effector T Cells ◽  
Infection Model ◽  
Myeloid Derived Suppressor Cells ◽  
Beneficial Effects ◽  
Joint Infections ◽  
Tnf Α

Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus infection are difficult to treat due to antibiotic resistance. It is known that the biofilms from methicillin-resistant S. aureus (MRSA) promote expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and benefit bacterial infections. This study finds that GMI, a fungal immunomodulatory peptide isolated from Ganoderma microsporum, suppresses MDSC expansion to promote the proliferation of cytotoxic T cells. The enhancement is likely attributed to increased expression of IL-6 and TNF-α and reduction in ROS expression. Similar beneficial effects of GMI on the suppression of MDSC expansion and IL-6 expression are also observed in the whole blood and reduces the accumulation of MDSCs in the infected bone region in a mouse PJI infection model. This study shows that GMI is potentially useful for treating S. aureus-induced PJIs.

Sign in / Sign up

Export Citation Format

Share Document