scholarly journals The Arabidopsis MIK2 receptor elicits immunity by sensing a conserved signature from phytocytokines and microbes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuguo Hou ◽  
Derui Liu ◽  
Shijia Huang ◽  
Dexian Luo ◽  
Zunyong Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dependent Manner ◽  
Receptor Kinase ◽  
Small Peptides ◽  
Robust Immune Response ◽  
Repeat Domain ◽  
Signature Peptides ◽  
Cytosolic Receptor

AbstractSessile plants encode a large number of small peptides and cell surface-resident receptor kinases, most of which have unknown functions. Here, we report that the Arabidopsis receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) recognizes the conserved signature motif of SERINE-RICH ENDOGENOUS PEPTIDEs (SCOOPs) from Brassicaceae plants as well as proteins present in fungal Fusarium spp. and bacterial Comamonadaceae, and elicits various immune responses. SCOOP signature peptides trigger immune responses and altered root development in a MIK2-dependent manner with a sub-nanomolar sensitivity. SCOOP12 directly binds to the extracellular leucine-rich repeat domain of MIK2 in vivo and in vitro, indicating that MIK2 is the receptor of SCOOP peptides. Perception of SCOOP peptides induces the association of MIK2 and the coreceptors SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3 (SERK3) and SERK4 and relays the signaling through the cytosolic receptor-like kinases BOTRYTIS-INDUCED KINASE 1 (BIK1) and AVRPPHB SUSCEPTIBLE1 (PBS1)-LIKE 1 (PBL1). Our study identifies a plant receptor that bears a dual role in sensing the conserved peptide motif from phytocytokines and microbial proteins via a convergent signaling relay to ensure a robust immune response.

scholarly journals Immune elicitation by sensing the conserved signature from phytocytokines and microbes via the Arabidopsis MIK2 receptor

2021 ◽  
Author(s):  
Shuguo Hou ◽  
Derui Liu ◽  
Shijia Huang ◽  
Dexian Luo ◽  
Zunyong Liu ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Receptor Kinase ◽  
Small Peptides ◽  
Robust Immune Response ◽  
Repeat Domain ◽  
Receptor Like Kinase ◽  
Signature Peptides ◽  
Cytosolic Receptor

ABSTRACTSessile plants encode a large number of small peptides and cell surface-resident receptor kinases, most of which have unknown functions. Here, we report that the Arabidopsis receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) recognizes the conserved signature motif of SERINE RICH ENDOGENOUS PEPTIDEs (SCOOPs) from plants as well as proteins present in fungal Fusarium spp. and bacterial Comamonadaceae, and elicits potent immune responses. SCOOP signature peptides trigger diverse immune and physiological responses in a MIK2-dependent manner with a sub-nanomolar sensitivity and directly bind to the extracellular leucine rich-repeat domain of MIK2 in vivo and in vitro, indicating that MIK2 is the receptor of SCOOP peptides. Perception of SCOOP peptides induces the association of MIK2 and the coreceptors SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3 (SERK3) and SERK4 and relays the signaling through the cytosolic receptor-like kinases BOTRYTIS-INDUCED KINASE 1 (BIK1) and AVRPPHB SUSCEPTIBLE1 (PBS1)-LIKE 1 (PBL1). Our study identified a unique plant receptor that bears a dual recognition capability sensing the conserved peptide motif from phytocytokines and microbial proteins via a convergent signaling relay to ensure a robust immune response.

scholarly journals Tolerogenic Splenic IDO+Dendritic Cells from the Mice Treated with Induced-Treg Cells Suppress Collagen-Induced Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Jie Yang ◽  
Yiming Yang ◽  
Huahua Fan ◽  
Hejian Zou
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Foxp3 Expression ◽  
Treated Group ◽  
Treg Cells ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Collagen Induced Arthritis

TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs)in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c+DCs, termed “DCiTreg,” expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activityin vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-βproduction was high in the DCiTreg-treated group. DCiTregalso induced new iTregsin vivo. Moreover, the inhibitory activity of DCiTregon CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCsin vivo.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

scholarly journals An XA21-Associated Kinase (OsSERK2) regulates immunity mediated by the XA21 and XA3 immune receptors

2013 ◽  
Author(s):  
Xuewei Chen ◽  
Shimin Zuo ◽  
Benjamin Schwessinger ◽  
Mawsheng Chern ◽  
Patrick Canlas ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Dependent Manner ◽  
Receptor Kinase ◽  
Immune Receptor ◽  
Immune Receptors ◽  
Yeast Two Hybrid System ◽  
Intracellular Domains ◽  
Activity Dependent

The rice XA21 immune receptor kinase and the structurally related XA3 receptor, confer immunity to Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight. Here we report the isolation of OsSERK2 (rice somatic embryogenesis receptor kinase 2) and demonstrate that OsSERK2 positively regulates immunity mediated by XA21 and XA3 as well as the rice immune receptor FLS2 (OsFLS2). Rice plants silenced for OsSerk2 display altered morphology and reduced sensitivity to the hormone brassinolide. OsSERK2 interacts with the intracellular domains of each immune receptor in the yeast-two-hybrid system in a kinase activity dependent manner. OsSERK2 undergoes bidirectional trans-phosphorylation with XA21 in vitro and forms a constitutive complex with XA21 in vivo. Taken together, these results demonstrate an essential role for OsSERK2 in the function of three rice immune receptors and suggest that direct interaction with the rice immune receptors is critical for their function.

scholarly journals Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin

2005 ◽  
Vol 201 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Cevayir Coban ◽  
Ken J. Ishii ◽  
Taro Kawai ◽  
Hiroaki Hemmi ◽  
Shintaro Sato ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Activation ◽  
Interleukin 1 ◽  
Innate Immune ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Innate Immune Activation

Malaria parasites within red blood cells digest host hemoglobin into a hydrophobic heme polymer, known as hemozoin (HZ), which is subsequently released into the blood stream and then captured by and concentrated in the reticulo-endothelial system. Accumulating evidence suggests that HZ is immunologically active, but the molecular mechanism(s) through which HZ modulates the innate immune system has not been elucidated. This work demonstrates that HZ purified from Plasmodium falciparum is a novel non-DNA ligand for Toll-like receptor (TLR)9. HZ activated innate immune responses in vivo and in vitro, resulting in the production of cytokines, chemokines, and up-regulation of costimulatory molecules. Such responses were severely impaired in TLR9−/− and myeloid differentiation factor 88 (MyD88)−/−, but not in TLR2, TLR4, TLR7, or Toll/interleukin 1 receptor domain–containing adaptor-inducing interferon β−/− mice. Synthetic HZ, which is free of the other contaminants, also activated innate immune responses in vivo in a TLR9-dependent manner. Chloroquine (CQ), an antimalarial drug, abrogated HZ-induced cytokine production. These data suggest that TLR9-mediated, MyD88-dependent, and CQ-sensitive innate immune activation by HZ may play an important role in malaria parasite–host interactions.

scholarly journals Small molecule allosteric inhibitors of RORγt block Th17-dependent inflammation and associated gene expression in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0248034
Author(s):  
Steven A. Saenz ◽  
Andrea Local ◽  
Tiffany Carr ◽  
Arvind Shakya ◽  
Shivsmriti Koul ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Th17 Cells ◽  
Human Tumor ◽  
Nuclear Hormone Receptor ◽  
Tumor Formation ◽  
Ductal Adenocarcinoma ◽  
Dependent Manner

Retinoic acid receptor-related orphan nuclear receptor (ROR) γt is a member of the RORC nuclear hormone receptor family of transcription factors. RORγt functions as a critical regulator of thymopoiesis and immune responses. RORγt is expressed in multiple immune cell populations including Th17 cells, where its primary function is regulation of immune responses to bacteria and fungi through IL-17A production. However, excessive IL-17A production has been linked to numerous autoimmune diseases. Moreover, Th17 cells have been shown to elicit both pro- and anti-tumor effects. Thus, modulation of the RORγt/IL-17A axis may represent an attractive therapeutic target for the treatment of autoimmune disorders and some cancers. Herein we report the design, synthesis and characterization of three selective allosteric RORγt inhibitors in preclinical models of inflammation and tumor growth. We demonstrate that these compounds can inhibit Th17 differentiation and maintenance in vitro and Th17-dependent inflammation and associated gene expression in vivo, in a dose-dependent manner. Finally, RORγt inhibitors were assessed for efficacy against tumor formation. While, RORγt inhibitors were shown to inhibit tumor formation in pancreatic ductal adenocarcinoma (PDAC) organoids in vitro and modulate RORγt target genes in vivo, this activity was not sufficient to delay tumor volume in a KP/C human tumor mouse model of pancreatic cancer.

scholarly journals A Novel Small Peptide Inhibitor of NFκB, RH10, Blocks Oxidative Stress-Dependent Phenotypes in Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jessica Gambardella ◽  
Michele Ciccarelli ◽  
Carmine Del Giudice ◽  
Antonella Fiordelisi ◽  
Matteo De Rosa ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Dependent Manner ◽  
Chemotherapeutic Drugs ◽  
Inhibit Tumor Growth ◽  
Small Peptides ◽  
Small Peptide ◽  
Stress Dependent ◽  
Dose Dependent

Background. The RH domain of GRK5 is an effective modulator of cancer growth through the inhibition of NFκB activity. The aim of this study was to identify the minimum effective sequence of RH that is still able to inhibit tumor growth and could be used as a peptide-based drug for therapy. Methods. Starting from the RH sequence, small peptides were cloned and tested in KAT-4 cells. The effects on NFκB signaling and its dependent phenotypes were evaluated by Western blot, TUNEL assay, proliferation assay, and angiogenesis in vitro. In vivo experiments were performed in KAT-4 xenografts in Balb/c nude mice. Results. A minimum RH ten amino acids long sequence (RH10) was able to interact with IκB, to increase IκB levels, to induce apoptosis, to inhibit KAT4-cell proliferation, NFκB activation, ROS production, and angiogenesis in vitro. In vivo, the peptide inhibited tumor growth in a dose-dependent manner. We also tested its effects in combination with chemotherapeutic drugs and radiotherapy. RH10 ameliorated the antitumor responses to cisplatin, doxorubicin, and ionizing radiation. Conclusion. Our data propose RH10 as a potential peptide-based drug to use for cancer treatment both alone or in combination with anticancer therapies.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

scholarly journals Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ai-Ling Tian ◽  
Qi Wu ◽  
Peng Liu ◽  
Liwei Zhao ◽  
Isabelle Martins ◽  
...  
Keyword(s):  
Stress Response ◽  
Immune Responses ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Serine Residue ◽  
Eif2α Phosphorylation ◽  
Lysosomotropic Agents ◽  
Cultured Human Cells

AbstractThe integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.

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