scholarly journals Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses

2008 ◽  
Vol 205 (1) ◽  
pp. 79-90 ◽  
Author(s):  
De Yang ◽  
Qian Chen ◽  
Shao Bo Su ◽  
Ping Zhang ◽  
Kahori Kurosaka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Secretory Protein ◽  
Myeloid Differentiation ◽  
Toll Like Receptor ◽  
T Helper ◽  
Adaptive Immune ◽  
Eosinophil Granule ◽  
Myeloid Differentiation Factor

Eosinophil-derived neurotoxin (EDN) is an eosinophil granule–derived secretory protein with ribonuclease and antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2–myeloid differentiation factor 88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independently of TLR1 or TLR6. When mice were immunized with ovalbumin (OVA) together with EDN or with EDN-treated OVA-loaded DCs, EDN enhanced OVA-specific T helper (Th)2-biased immune responses as indicated by predominant production of OVA-specific interleukin (IL)-5, IL-6, IL-10, and IL-13, as well as higher levels of immunoglobulin (Ig)G1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen-specific immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen-specific Th2 immune responses.

scholarly journals MYCOBACTERIUM TUBERCULOSIS SISTEM IMUN ALAMIAH TERKAIT PENERIMANYA

2016 ◽  
Vol 19 (1) ◽  
pp. 45
Author(s):  
Jusak Nugraha
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokine ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Myeloid Differentiation ◽  
Toll Like Receptor ◽  
Protective Function ◽  
Adaptive Immune ◽  
Tnf Α ◽  
Myeloid Differentiation Factor

Various attemp to investigate immune response towards tuberculosis has been done in order to eradicate or to make vaccination against tuberculosis (TB) effectively. Recently it is known that innate immunity has an important role in immunity to TB despite adaptive immune response, because it was proved that adaptive immune response alone was not sufficient to eradicate this microorganism thoroughly and completely in patient’s body. After Toll-Like Receptor (TLR) was found in the end of the 20th century, many progresses has been obtained in understanding about the activation of this innate immune response. But it is still needed to understand more deeply in the immune response to M. tuberculosis to lead the development of therapy or vaccination that bring into more precise target. The activation through TLR by parts of Mycobacterium induce cytoplasm protein adaptor MyD88 (Myeloid Differentiation factor 88). MyD88 has the function to activate NF- κB and secrete pro-inflammatory cytokine such as TNF-α, IL-6, IL-12. Involvement of MyD88 is not solely dependent of TLR2 receptor and there are another pathways to induce protective function of immunocompetent cells in TB.

scholarly journals Recent Advances in Good Manufacturing Practice-Grade Generation of Dendritic Cells

2020 ◽  
Vol 47 (6) ◽  
pp. 454-463
Author(s):  
Sarah Cunningham ◽  
Holger Hackstein
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Good Manufacturing Practice ◽  
Clinical Applications ◽  
Small Scale ◽  
Adaptive Immune ◽  
Recent Advances ◽  
Experimental Approaches ◽  
Key Features

Dendritic cells (DCs) are pivotal regulators of immune responses, specialized in antigen presentation and bridging the gap between the innate and adaptive immune system. Due to these key features, DCs have become a pillar of the continuously growing field of cellular therapies. Here we review recent advances in good manufacturing practice strategies and their individual specificities in relation to DC production for clinical applications. These take into account both small-scale experimental approaches as well as automated systems for patient care.

scholarly journals Toll-like Receptors Induce a Phagocytic Gene Program through p38

2003 ◽  
Vol 199 (1) ◽  
pp. 81-90 ◽  
Author(s):  
Sean E. Doyle ◽  
Ryan M. O'Connell ◽  
Gustavo A. Miranda ◽  
Sagar A. Vaidya ◽  
Edward K. Chow ◽  
...  
Keyword(s):  
Immune Responses ◽  
Interleukin 1 ◽  
Innate Immune ◽  
Myeloid Differentiation ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Evolutionarily Conserved ◽  
Myeloid Differentiation Factor ◽  
The Relationship ◽  
Number Of Bacteria

Toll-like receptor (TLR) signaling and phagocytosis are hallmarks of macrophage-mediated innate immune responses to bacterial infection. However, the relationship between these two processes is not well established. Our data indicate that TLR ligands specifically promote bacterial phagocytosis, in both murine and human cells, through induction of a phagocytic gene program. Importantly, TLR-induced phagocytosis of bacteria was found to be reliant on myeloid differentiation factor 88–dependent signaling through interleukin-1 receptor–associated kinase-4 and p38 leading to the up-regulation of scavenger receptors. Interestingly, individual TLRs promote phagocytosis to varying degrees with TLR9 being the strongest and TLR3 being the weakest inducer of this process. We also demonstrate that TLR ligands not only amplify the percentage of phagocytes uptaking Escherichia coli, but also increase the number of bacteria phagocytosed by individual macrophages. Taken together, our data describe an evolutionarily conserved mechanism by which TLRs can specifically promote phagocytic clearance of bacteria during infection.

scholarly journals Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing

2009 ◽  
Vol 206 (6) ◽  
pp. 1339-1350 ◽  
Author(s):  
Ryutaro Fukui ◽  
Shin-ichiroh Saitoh ◽  
Fumi Matsumoto ◽  
Hiroko Kozuka-Hata ◽  
Masaaki Oyama ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Nucleic Acids ◽  
Toll Like Receptor ◽  
Autoantibody Production ◽  
Adaptive Immune ◽  
Tlr9 Ligand ◽  
Membrane Spanning ◽  
Protein Complementation ◽  
Tlr7 Ligand

Toll-like receptors (TLRs) 3, 7, and 9 recognize microbial nucleic acids in endolysosomes and initiate innate and adaptive immune responses. TLR7/9 in dendritic cells (DCs) also respond to self-derived RNA/DNA, respectively, and drive autoantibody production. Remarkably, TLR7 and 9 appear to have mutually opposing, pathogenic or protective, impacts on lupus nephritis in MRL/lpr mice. Little is known, however, about the contrasting relationship between TLR7 and 9. We show that TLR7 and 9 are inversely linked by Unc93B1, a multiple membrane-spanning endoplasmic reticulum (ER) protein. Complementation cloning with a TLR7-unresponsive but TLR9-responsive cell line revealed that amino acid D34 in Unc93B1 repressed TLR7-mediated responses. D34A mutation rendered Unc93B1-deficient DCs hyperresponsive to TLR7 ligand but hyporesponsive to TLR9 ligand, with TLR3 responses unaltered. Unc93B1 associates with and delivers TLR7/9 from the ER to endolysosomes for ligand recognition. The D34A mutation up-regulates Unc93B1 association with endogenous TLR7 in DCs, whereas Unc93B1 association with TLR9 was down-regulated by the D34A mutation. Consistently, the D34A mutation up-regulated ligand-induced trafficking of TLR7 but down-regulated that of TLR9. Collectively, TLR response to nucleic acids in DCs is biased toward DNA-sensing by Unc93B1.

scholarly journals Mice Plasmacytoid Dendritic Cells Were Activated by Lipopolysaccharides Through Toll-Like Receptor 4/Myeloid Differentiation Factor 2

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zhang ◽  
Eun-Koung An ◽  
Juyoung Hwang ◽  
Jun-O Jin
Keyword(s):  
Dendritic Cells ◽  
B Cells ◽  
Viral Infections ◽  
Intraperitoneal Administration ◽  
Plasmacytoid Dendritic Cells ◽  
Myeloid Differentiation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Differentiation Factor ◽  
Myeloid Differentiation Factor

Plasmacytoid dendritic cells (pDCs) are known to respond to viral infections. However, the activation of pDCs by bacterial components such as lipopolysaccharides (LPS) has not been well studied. Here, we found that pDCs, conventional dendritic cells (cDCs), and B cells express high levels of toll-like receptor 4 (TLR4), a receptor for LPS. Moreover, LPS could effectively bind to not only cDCs but also pDCs and B cells. Intraperitoneal administration of LPS promoted activation of splenic pDCs and cDCs. LPS treatment led to upregulation of interferon regulatory factor 7 (IRF7) and induced production of interferon-alpha (IFN-α) in splenic pDCs. Furthermore, LPS-dependent upregulation of co-stimulatory molecules in pDCs did not require the assistance of other immune cells, such as cDCs. However, the production levels of IFN-α were decreased in cDC-depleted splenocytes, indicating that cDCs may contribute to the enhancement of IFN-α production in pDCs. Finally, we showed that activation of pDCs by LPS requires the TLR4 and myeloid differentiation factor 2 (MD2) signaling pathways. Thus, these results demonstrate that the gram-negative component LPS can directly stimulate pDCs via TLR4/MD2 stimulation in mice.

scholarly journals A protein associated with Toll-like receptor (TLR) 4 (PRAT4A) is required for TLR-dependent immune responses

2007 ◽  
Vol 204 (12) ◽  
pp. 2963-2976 ◽  
Author(s):  
Koichiro Takahashi ◽  
Takuma Shibata ◽  
Sachiko Akashi-Takamura ◽  
Takashi Kiyokawa ◽  
Yasutaka Wakabayashi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Poly I:C ◽  
Toll Like Receptor ◽  
T Helper ◽  
Surface Molecules ◽  
Adaptive Immune ◽  
And Function ◽  
Tlr3 Ligand Poly

Immune cells express multiple Toll-like receptors (TLRs) that are concomitantly activated by a variety of pathogen products. Although there is presumably a need to coordinate the expression and function of TLRs in individual cells, little is known about the mechanisms governing this process. We show that a protein associated with TLR4 (PRAT4A) is required for multiple TLR responses. PRAT4A resides in the endoplasmic reticulum, and PRAT4A knockdown inhibited trafficking of TLR1 and TLR4 to the cell surface and ligand-induced trafficking of TLR9 to lysosomes. Other cell-surface molecules were expressed normally on immunocytes from PRAT4A−/− mice. There was impaired cytokine production to TLR ligands, except to the TLR3 ligand poly(I:C), and to whole bacteria. Activation of antigen-specific T helper type 1 responses were also defective. Moreover, PRAT4A−/− bone marrow chimeric mice were resistant to lipopolysaccharide-induced sepsis. These results suggest that PRAT4A regulates the subcellular distribution and response of multiple TLRs and is required for both innate and adaptive immune responses.

Select hyperactivating NLRP3 ligands enhance the TH1- and TH17-inducing potential of human type 2 conventional dendritic cells

2021 ◽  
Vol 14 (680) ◽  
pp. eabe1757
Author(s):  
Lukas Hatscher ◽  
Christian H. K. Lehmann ◽  
Ariawan Purbojo ◽  
Constantin Onderka ◽  
Chunguang Liang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Vaccine Development ◽  
Inflammatory Diseases ◽  
Toll Like Receptor ◽  
T Helper ◽  
Conventional Type ◽  
Prime Target

The detection of microorganisms and danger signals by pattern recognition receptors on dendritic cells (DCs) and the consequent formation of inflammasomes are pivotal for initiating protective immune responses. Although the activation of inflammasomes leading to secretion of the cytokine IL-1β is typically accompanied by pyroptosis (an inflammatory form of lytic programmed cell death), some cells can survive and exist in a state of hyperactivation. Here, we found that the conventional type 2 DC (cDC2) subset is the major human DC subset that is transcriptionally and functionally poised for inflammasome formation and response without pyroptosis. When cDC2 were stimulated with ligands that relatively weakly activated the inflammasome, the cells did not enter pyroptosis but instead secreted IL-12 family cytokines and IL-1β. These cytokines induced prominent T helper type 1 (TH1) and TH17 responses that were superior to those seen in response to Toll-like receptor (TLR) stimulation alone or to stronger, classical inflammasome ligands. These findings not only define the human cDC2 subpopulation as a prime target for the treatment of inflammasome-dependent inflammatory diseases but may also inform new approaches for adjuvant and vaccine development.

Signaling through Toll-like receptor 3 and Dectin-1 potentiates the capability of human monocyte-derived dendritic cells to promote T-helper 1 and T-helper 17 immune responses

Cytotherapy ◽  
2012 ◽  
Vol 14 (5) ◽  
pp. 598-607 ◽  
Author(s):  
Ana Dragicevic ◽  
Tanja Dzopalic ◽  
Sasa Vasilijic ◽  
Dragana Vucevic ◽  
Sergej Tomic ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Human Monocyte ◽  
Toll Like Receptor ◽  
T Helper ◽  
T Helper 1 ◽  
T Helper 17
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