Innate immune functions of plasmacytoid dendritic cells

2007 ◽  
Vol 19 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Wei Cao ◽  
Yong-Jun Liu
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Innate Immune ◽  
Immune Functions

scholarly journals Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 456 ◽  
Author(s):  
Philippe Saas ◽  
Alexis Varin ◽  
Sylvain Perruche ◽  
Adam Ceroi
Keyword(s):  
Dendritic Cells ◽  
Lipid Metabolism ◽  
Nuclear Receptors ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Plasmacytoid Dendritic Cell ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Cells ◽  
Immune Functions

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

scholarly journals Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ

2006 ◽  
Vol 177 (11) ◽  
pp. 7510-7514 ◽  
Author(s):  
Jennifer M. Lund ◽  
Melissa M. Linehan ◽  
Norifumi Iijima ◽  
Akiko Iwasaki
Keyword(s):  
Dendritic Cells ◽  
Viral Infection ◽  
Plasmacytoid Dendritic Cells ◽  
Innate Immune ◽  
Cutting Edge ◽  
Immune Protection

Rapamycin Inhibits Innate and Adaptive Immune Functions of Human Plasmacytoid Dendritic Cells

2012 ◽  
Vol 94 (10S) ◽  
pp. 455
Author(s):  
P. P. Boor ◽  
S. Mancham ◽  
L. W. van der Laan ◽  
H. J. Metselaar ◽  
J. Kwekkeboom
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Immune Functions ◽  
Adaptive Immune

scholarly journals TLR7 stimulation in human plasmacytoid dendritic cells leads to the induction of early IFN-inducible genes in the absence of type I IFN

Blood ◽  
2009 ◽  
Vol 114 (9) ◽  
pp. 1794-1802 ◽  
Author(s):  
Jérémy Di Domizio ◽  
Ariane Blum ◽  
Maighread Gallagher-Gambarelli ◽  
Jean-Paul Molens ◽  
Laurence Chaperot ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
P38mapk Pathway ◽  
Inducible Genes ◽  
Level Production ◽  
Early Phases ◽  
Tlr7 Stimulation

On recognition of influenza virus (Flu) by TLR7, plasmacytoid dendritic cells (pDCs) produce type I IFN in significant amounts. Synthetic TLR7 ligands induce the maturation of pDCs, as evidenced by the expression of costimulatory molecules and the production of proinflammatory cytokines; however, they induce only low-level production of IFN-α. To dissect the TLR7 signaling in pDCs and how these different profiles are induced, we studied the effects of 2 TLR7 ligands (Flu and CL097) on the activation of blood-isolated pDCs and the human GEN2.2 pDC cell line. Type I IFN production by pDCs correlates with differential interferon regulatory factor 7 (IRF7) translocation into the nucleus induced by the 2 TLR7 ligands. Surprisingly, with both activators we nevertheless observed the rapid expression of the IFN-inducible genes mxa, cxcl10, and trail within 4 hours of stimulation. This expression, controlled by STAT1 phosphorylation, was independent of type I IFN. STAT1 activation was found to be strictly dependent on the PI3K-p38MAPK pathway, showing a new signaling pathway leading to rapid expression of IFN-inducible genes after TLR7 triggering. Thus, pDCs, through this unusual TLR7 signaling, have the capacity to promptly respond to viral infection during the early phases of the innate immune response.

scholarly journals A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes

2017 ◽  
Vol 114 (8) ◽  
pp. 1988-1993 ◽  
Author(s):  
Hong Zhang ◽  
Josh D. Gregorio ◽  
Toru Iwahori ◽  
Xiangyue Zhang ◽  
Okmi Choi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Activation ◽  
Plasmacytoid Dendritic Cells ◽  
T Cell Proliferation ◽  
Type I ◽  
Type I Ifn ◽  
Immune Functions ◽  
B Cell Activation ◽  
Cpg Oligonucleotides ◽  
B And T Lymphocytes

Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2hiCD5+CD81+pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34+progenitors. These CD2hiCD5+CD81+cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. However, their gene expression profile is distinct, and they produce little or no type I IFN upon stimulation with CpG oligonucleotides, likely due to their diminished expression of IFN regulatory factor 7. A similar population of CD5+CD81+pDCs is present in mice and also does not produce type I IFN after CpG stimulation. In contrast to conventional CD5−CD81−pDCs, human CD5+CD81+pDCs are potent stimulators of B-cell activation and antibody production and strong inducers of T-cell proliferation and Treg formation. These findings reveal the presence of a discrete pDC population that does not produce type I IFN and yet mediates important immune functions previously attributed to all pDCs.

Ontogeny and innate properties of neonatal dendritic cells

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 585-591 ◽  
Author(s):  
Cheng-Ming Sun ◽  
Laurence Fiette ◽  
Myriam Tanguy ◽  
Claude Leclerc ◽  
Richard Lo-Man
Keyword(s):  
Dendritic Cells ◽  
Early Life ◽  
Innate Immune ◽  
Type I ◽  
Adult Size ◽  
Immune Functions ◽  
High Susceptibility ◽  
Major Histocompatibility Complexes ◽  
Plasmacytoid Dcs

Abstract We investigated whether a developmental immaturity of the dendritic cells (DCs) compartment could contribute to the high susceptibility to infections observed in newborns. DCs are among the first cells to colonize the spleen, but the ontogeny of DC subsets follows distinct steps. At birth, plasmacytoid DCs and CD4-CD8α- DCs are found in the spleen, whereas CD8α+ and CD4+ DCs are not present. Then, the CD8α+ DC compartment quickly develops and reaches an adult size by day 7, whereas the CD4+ DC compartment slowly increases to become predominant by the age of 3 weeks. The production of interleukin (IL)–12p70 by DCs is particularly efficient after birth, reflecting the stronger capacity of the neonatal CD8α- DCs to secrete IL-12 compared with its adult counterpart. Like-wise, neonatal DCs produced type I and II interferons. In vivo, following microbial stimulation, up-regulation of major histocompatibility complexes (MHCs) and of costimulatory molecules on DCs was induced clearly showing the activation of neonatal DCs in the neonatal environment. Therefore, despite a markedly different DC subset composition in early life compared with the adult DC compartment, neonatal DCs are fully competent in their innate immune functions.

scholarly journals Immune responses of macrophages and dendritic cells regulated by mTOR signalling

2013 ◽  
Vol 41 (4) ◽  
pp. 927-933 ◽  
Author(s):  
Karl Katholnig ◽  
Monika Linke ◽  
Ha Pham ◽  
Markus Hengstschläger ◽  
Thomas Weichhart
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Immune Responses ◽  
Inflammatory Mediators ◽  
Cellular Response ◽  
Mtor Pathway ◽  
The Body ◽  
Innate Immune ◽  
Immune Functions ◽  
Tissue Remodelling

The innate myeloid immune system is a complex network of cells that protect against disease by identifying and killing pathogens and tumour cells, but it is also implicated in homoeostatic mechanisms such as tissue remodelling and wound healing. Myeloid phagocytes such as monocytes, macrophages or dendritic cells are at the basis of controlling these immune responses in all tissues of the body. In the present review, we summarize recent studies demonstrating that mTOR [mammalian (or mechanistic) target of rapamycin] regulates innate immune reactions in macrophages and dendritic cells. The mTOR pathway serves as a decision maker to control the cellular response to pathogens and tumours by regulating the expression of inflammatory mediators such as cytokines, chemokines or interferons. In addition to various in vivo mouse models, kidney transplant patients under mTOR inhibitor therapy allowed the elucidation of important innate immune functions regulated by mTOR in humans. The role of the mTOR pathway in macrophages and dendritic cells enhances our understanding of the immune system and suggests new therapeutic avenues for the regulation of pro- versus anti-inflammatory mediators with potential relevance to cancer therapy, the design of novel adjuvants and the control of distinct infectious and autoimmune diseases.

scholarly journals The role of STIM and ORAI proteins in phagocytic immune cells

2016 ◽  
Vol 310 (7) ◽  
pp. C496-C508 ◽  
Author(s):  
Nicolas Demaurex ◽  
Paula Nunes
Keyword(s):  
Dendritic Cells ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Toxic Substances ◽  
Immune Functions ◽  
Phagocytic Cells ◽  
Major Pathway ◽  
Physiological Impact ◽  
Molecular Components

Phagocytic cells, such as neutrophils, macrophages, and dendritic cells, migrate to sites of infection or damage and are integral to innate immunity through two main mechanisms. The first is to directly neutralize foreign agents and damaged or infected cells by secreting toxic substances or ingesting them through phagocytosis. The second is to alert the adaptive immune system through the secretion of cytokines and the presentation of the ingested materials as antigens, inducing T cell maturation into helper, cytotoxic, or regulatory phenotypes. While calcium signaling has been implicated in numerous phagocyte functions, including differentiation, maturation, migration, secretion, and phagocytosis, the molecular components that mediate these Ca2+signals have been elusive. The discovery of the STIM and ORAI proteins has allowed researchers to begin clarifying the mechanisms and physiological impact of store-operated Ca2+entry, the major pathway for generating calcium signals in innate immune cells. Here, we review evidence from cell lines and mouse models linking STIM and ORAI proteins to the control of specific innate immune functions of neutrophils, macrophages, and dendritic cells.

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