scholarly journals Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells

2008 ◽  
Vol 205 (4) ◽  
pp. 869-882 ◽  
Author(s):  
Mirjam Kool ◽  
Thomas Soullié ◽  
Menno van Nimwegen ◽  
Monique A.M. Willart ◽  
Femke Muskens ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Uric Acid ◽  
Lymph Node ◽  
Danger Signal ◽  
Th2 Response ◽  
Inflammatory Monocytes ◽  
Cellular And Humoral Immunity ◽  
Inflammatory Dendritic Cells ◽  
Deficient Mice

Alum (aluminum hydroxide) is the most widely used adjuvant in human vaccines, but the mechanism of its adjuvanticity remains unknown. In vitro studies showed no stimulatory effects on dendritic cells (DCs). In the absence of adjuvant, Ag was taken up by lymph node (LN)–resident DCs that acquired soluble Ag via afferent lymphatics, whereas after injection of alum, Ag was taken up, processed, and presented by inflammatory monocytes that migrated from the peritoneum, thus becoming inflammatory DCs that induced a persistent Th2 response. The enhancing effects of alum on both cellular and humoral immunity were completely abolished when CD11c+ monocytes and DCs were conditionally depleted during immunization. Mechanistically, DC-driven responses were abolished in MyD88-deficient mice and after uricase treatment, implying the induction of uric acid. These findings suggest that alum adjuvant is immunogenic by exploiting “nature's adjuvant,” the inflammatory DC through induction of the endogenous danger signal uric acid.

scholarly journals Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance

1999 ◽  
Vol 189 (4) ◽  
pp. 627-636 ◽  
Author(s):  
Caroline Robert ◽  
Robert C. Fuhlbrigge ◽  
J. David Kieffer ◽  
Seyoum Ayehunie ◽  
Richard O. Hynes ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Flow Conditions ◽  
Cutaneous Inflammation ◽  
New Perspective ◽  
Blocking Antibodies ◽  
Deficient Mice

The goal of this study was to determine the mechanisms by which dendritic cells (DCs) in blood could interact with endothelium, a prerequisite to extravasation into tissues. Our results indicate that DCs express both HECA-452–reactive and nonreactive isoforms of P-selectin glycoprotein ligand 1 (PSGL-1) and can tether and roll efficiently on E- and P-selectin under flow conditions in vitro. Freshly isolated blood DCs were further observed to roll continuously along noninflamed murine dermal endothelium in vivo. This interaction is strictly dependent on endothelial selectins, as shown by experiments with blocking antibodies and with E- and P-selectin–deficient mice. We hypothesize that DCs in blood are constitutively poised at the interface of blood and skin, ready to extravasate upon induction of inflammation, and we showed that cutaneous inflammation results in a rapid recruitment of DCs from the blood to tissues. We propose that this is an important and previously unappreciated element of immunosurveillance.

scholarly journals Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies.

1987 ◽  
Vol 166 (6) ◽  
pp. 1654-1667 ◽  
Author(s):  
S E Macatonia ◽  
S C Knight ◽  
A J Edwards ◽  
S Griffiths ◽  
P Fryer
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
T Lymphocytes ◽  
Langerhans Cells ◽  
Fluorescein Isothiocyanate ◽  
Morphological Studies ◽  
Draining Lymph Node ◽  
Two Populations ◽  
Skin Painting

We have examined the cells involved in the development of contact sensitivity to FITC in CBA mice. After skin painting with antigen, the number of dendritic cells (DC) in the draining lymph nodes increased by 30 min, was maximal at 48 h, and returned to normal by 6 d. Derivation of some DC from Langerhans' cells of the skin was indicated from the presence of Birbeck granules observed in some DC isolated 24 h after skin painting. The DC acquired FITC and by 8 h there were two populations, one highly fluorescent and the other less fluorescent. The highly fluorescent cells were present between 8 h and 3 d after sensitization, and during this period the DC were potent at initiating primary proliferative responses of normal syngeneic T lymphocytes in vitro. Between days 3 and 5 the numbers of lymphocytes in the draining lymph node increased. During this period purified T lymphocytes did not express detectable levels of antigen, but enriched B cell populations expressed antigen transiently on day 1, 2, or 3 after exposure to antigen. The results showed that, during a 3-d period after exposure to antigen, DC expressed antigen and stimulated T cell proliferation. We speculate that low amounts of FITC binding selectively to veiled cells or lymph node DC in the first hours after exposure to antigen are not immunogenic but that Langerhans' cells acquire high levels of antigen, enter the nodes, and initiate immune responses.

Dendritic cell-derived IL-2 production is regulated by IL-15 in humans and in mice

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 697-702 ◽  
Author(s):  
Sonia Feau ◽  
Valeria Facchinetti ◽  
Francesca Granucci ◽  
Stefania Citterio ◽  
David Jarrossay ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Interleukin 2 ◽  
Adaptive Immune ◽  
Deficient Mice ◽  
Mouse System

Abstract Dendritic cells (DCs) are involved in the initiation and regulation of innate and adaptive immune responses. Several molecular mechanisms regulate these diverse DC functions, and we have previously reported that mouse dendritic cells (mDCs) can produce interleukin-2 (IL-2) in vitro and in vivo, in response to microbial activation and T-cell-mediated stimuli. This property is shared by different DC subtypes, including Langerhans cells. Here we show that, on appropriate stimulation, human DCs, both plasmacytoid and myeloid subtypes, also express IL-2. Interestingly, the production of IL-2 by myeloid DCs is induced by T-cell-mediated stimuli and depends on the presence of IL-15. The key role of this cytokine in regulating IL-2 production was also confirmed in the mouse system. In particular, we could show that DCs from IL-15-deficient mice were strongly impaired in the ability to produce IL-2 after interactions with different microbial stimuli. Our results indicate that DC-produced IL-2 is tightly coregulated with the expression of IL-15.

INTERDEPENDENCE BETWEEN THE PHENOTYPE OF DENDRITIC CELLS AND AMOUNTS OF BLOOD PROINFLAMMATORY MONOCYTES IN PATIENTS WITH KIDNEY CANCER

2019 ◽  
Vol 21 (4) ◽  
pp. 689-702
Author(s):  
A. A. Savchenko ◽  
A. G. Borisov ◽  
I. V. Kudryavtsev ◽  
A. V. Moshev
Keyword(s):  
Dendritic Cells ◽  
Kidney Cancer ◽  
Peripheral Blood ◽  
Receptor Expression ◽  
Autologous Serum ◽  
Autologous Tumor ◽  
Blood Monocytes ◽  
Inflammatory Monocytes ◽  
Antigen Presenting

The aim of the study was to investigate an interdependence between the phenotype of dendritic cells (DC) differentiated from monocytes and the number of pro-inflammatory monocytes in peripheral blood of patients with kidney cancer (KC). The study involved 28 patients at the age of 40-55 years suffering with KC (Т3N0М0, clear cell type) before surgical treatment. The diagnosis was verified histologically. 31 healthy agematched persons were examined as a control group. Mononuclear cells were isolated from heparinized venous blood by centrifugation in a Histopaque®-1077 density gradient followed by plastic adsorption in RPMI 1640 medium supplied with 10% autologous serum. Immature DCs (iDCs) were generated from blood monocytes by culturing for 5 days with GM-CSF and IFNα. Activation of DCs (mDCs) was induced by incubation with the tumor cell lysate and TNFα, followed by incubation for 48 hours. A tumor fragment was used to prepare the lysate of autologous tumor cells. Phenotyping of blood monocytes and DC at various maturation stages was performed by flow cytometry. The numbers of CD14+CD16+ monocytes in peripheral blood of KC patients were decreased (up to 42% of the total monocyte level) against the control ranges. In this regard, the analysis of the dependence between the phenotype of DCs differentiated from monocytes and the number of pro-inflammatory blood monocytes was carried out by comparing the groups with a high content of pro-inflammatory monocytes in the blood in KC patients (> 42%, near-control range) and low content (resp., < 42%). We have found that the contents of tolerogenic iDC in cell culture are increased in KC patients with low amounts of pro-inflammatory monocytes in blood (< 42%). A relatively increased expression of antigen-presenting and co-stimulatory molecules proved to be the specific feature of iDC phenotype in patients with high contents (> 42%) of proinflammatory monocytes in blood. The phenotype of dendritic cells in KC patients with different content of proinflammatory monocytes during maturation/activation showed more differences. In the patients with low levels of pro-inflammatory monocytes, the cell pool of in vitro maturing DCs was characterized by low level of CD86 and HLA-DR receptor expression, thus reflecting a weak co-stimulating and antigen-presenting activity. In the patients with high levels of pro-inflammatory monocytes in blood, the in vitro activated DCs showed higher level of functional activity using the above markers. The revealed differences in the DC phenotype and interrelations with amounts of blood monocyte subpopulations in KC patients may presume the programmed cell differentiation mechanisms depending on the microenvironment, under pathogenic conditions (i.e., in presence of malignant tumor growth).

scholarly journals IL-15Rα-Independent IL-15 Signaling in Non-NK Cell-Derived IFNγ Driven Control of Listeria monocytogenes

2021 ◽  
Vol 12 ◽  
Author(s):  
Madhuparna Nandi ◽  
Mitterrand Muamba Moyo ◽  
Sakina Orkhis ◽  
Jeanne Masunga Faida Mobulakani ◽  
Marc-André Limoges ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Immune Cell ◽  
Nk Cell ◽  
Myeloid Cell ◽  
Inflammatory Monocytes ◽  
Receptor Chain ◽  
Bacterial Uptake ◽  
Deficient Mice

Interleukin-15, produced by hematopoietic and parenchymal cells, maintains immune cell homeostasis and facilitates activation of lymphoid and myeloid cell subsets. IL-15 interacts with the ligand-binding receptor chain IL-15Rα during biosynthesis, and the IL-15:IL-15Rα complex is trans-presented to responder cells that express the IL-2/15Rβγc complex to initiate signaling. IL-15-deficient and IL-15Rα-deficient mice display similar alterations in immune cell subsets. Thus, the trimeric IL-15Rαβγc complex is considered the functional IL-15 receptor. However, studies on the pathogenic role of IL-15 in inflammatory and autoimmune diseases indicate that IL-15 can signal independently of IL-15Rα via the IL-15Rβγc dimer. Here, we compared the ability of mice lacking IL-15 (no signaling) or IL-15Rα (partial/distinct signaling) to control Listeria monocytogenes infection. We show that IL-15-deficient mice succumb to infection whereas IL-15Rα-deficient mice clear the pathogen as efficiently as wildtype mice. IL-15-deficient macrophages did not show any defect in bacterial uptake or iNOS expression in vitro. In vivo, IL-15 deficiency impaired the accumulation of inflammatory monocytes in infected spleens without affecting chemokine and pro-inflammatory cytokine production. The inability of IL-15-deficient mice to clear L. monocytogenes results from impaired early IFNγ production, which was not affected in IL-15Rα-deficient mice. Administration of IFNγ partially enabled IL-15-deficient mice to control the infection. Bone marrow chimeras revealed that IL-15 needed for early bacterial control can originate from both hematopoietic and non-hematopoietic cells. Overall, our findings indicate that IL-15-dependent IL-15Rα-independent signaling via the IL-15Rβγc dimeric complex is necessary and sufficient for the induction of IFNγ from sources other than NK/NKT cells to control bacterial pathogens.

scholarly journals In vivo Priming of T Cells with in vitro Pulsed Dendritic Cells: Popliteal Lymph Node Assay

BIO-PROTOCOL ◽  
2017 ◽  
Vol 7 (17) ◽  
Author(s):  
Songjie Cai ◽  
Masayuki Fujino ◽  
Lina Lu ◽  
Xiao-Kang Li
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Popliteal Lymph Node ◽  
Popliteal Lymph Node Assay

scholarly journals Fate mapping reveals origin and dynamics of lymph node follicular dendritic cells

2014 ◽  
Vol 211 (6) ◽  
pp. 1109-1122 ◽  
Author(s):  
Meryem Jarjour ◽  
Audrey Jorquera ◽  
Isabelle Mondor ◽  
Stephan Wienert ◽  
Priyanka Narang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
Cell Function ◽  
Ex Vivo ◽  
Fate Mapping ◽  
Follicular Dendritic Cells ◽  
Critical Function ◽  
Subcapsular Sinus ◽  
Follicular Dendritic

Follicular dendritic cells (FDCs) regulate B cell function and development of high affinity antibody responses but little is known about their biology. FDCs associate in intricate cellular networks within secondary lymphoid organs. In vitro and ex vivo methods, therefore, allow only limited understanding of the genuine immunobiology of FDCs in their native habitat. Herein, we used various multicolor fate mapping systems to investigate the ontogeny and dynamics of lymph node (LN) FDCs in situ. We show that LN FDC networks arise from the clonal expansion and differentiation of marginal reticular cells (MRCs), a population of lymphoid stromal cells lining the LN subcapsular sinus. We further demonstrate that during an immune response, FDCs accumulate in germinal centers and that neither the recruitment of circulating progenitors nor the division of local mature FDCs significantly contributes to this accumulation. Rather, we provide evidence that newly generated FDCs also arise from the proliferation and differentiation of MRCs, thus unraveling a critical function of this poorly defined stromal cell population.

scholarly journals Natural ligands of the B cell adhesion molecule CD22 beta can be masked by 9-O-acetylation of sialic acids.

1994 ◽  
Vol 126 (2) ◽  
pp. 549-562 ◽  
Author(s):  
E R Sjoberg ◽  
L D Powell ◽  
A Klein ◽  
A Varki
Keyword(s):  
Dendritic Cells ◽  
Lymph Node ◽  
B Cells ◽  
B Cell ◽  
Sialic Acids ◽  
Lymphoid Cells ◽  
Side Chain ◽  
Adhesion Assay ◽  
In Vitro Adhesion

CD22 beta is a B cell-restricted phosphoprotein expressed on the surface of mature resting B cells. It mediates interactions with other cells partly or exclusively via recognition of alpha 2-6-linked sialic acids on glycoconjugates. The sialylated N-linked oligosaccharides recognized best by CD22 beta are common to many glycoproteins, suggesting that additional regulatory mechanisms may exist. Since the exocyclic side chain of sialic acid is required for recognition, we explored the effects of a naturally occurring modification of the side chain, 9-O-acetylation. Semisynthetic N-linked oligosaccharides terminating with 9-O-acetylated, alpha 2-6-linked sialic acids showed markedly reduced binding to CD22 beta relative to their non-O-acetylated counterparts. Murine lymphoid cells were probed for natural CD22 beta ligands that might be O-acetylated using recombinant soluble forms of CD22 beta (CD22 beta Rg) and influenza C esterase (CHE-Fc, which specifically removes 9-O-acetyl esters from sialic acids). By flow cytometry analysis, CD22 beta Rg binding to splenic B cells and a subset of T cells was increased by pretreatment with CHE-Fc, indicating that some potential CD22 beta ligands are naturally "masked" by 9-O-acetylation. Unmasking of these CD22 beta ligands by removal of 9-O-acetyl esters from intact splenocytes substantially increases their CD22 beta-dependent adhesion in an in vitro adhesion assay. Probing of murine lymphoid tissue sections by CD22 beta Rg and CHE-Fc treatment demonstrates regionally restricted and differentially expressed patterns of distribution between masked and unmasked ligands. For example, lymph node-associated follicular B cells express high levels of CD22 beta ligands, none of which are masked by 9-O-acetylation. In contrast, the ligands on lymph node-associated dendritic cells are almost completely masked by 9-O-acetylation, suggesting that masking may regulate interactions between CD22 beta-positive B cells and dendritic cells. In the thymus, only medullary cells express CD22 beta ligands, and a significant portion of these are masked by 9-O-acetylation, particularly at the cortical-medullary junction. Thus, 9-O-acetylation of sialic acids on immune cells is in a position to negatively regulate CD22 beta adhesion events in a manner depending on both cell type and tissue localization.

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