scholarly journals Exposure to Bacillus anthracis Capsule Results in Suppression of Human Monocyte-Derived Dendritic Cells

2014 ◽  
Vol 82 (8) ◽  
pp. 3405-3416 ◽  
Author(s):  
Tanya M. Jelacic ◽  
Donald J. Chabot ◽  
Joel A. Bozue ◽  
Steven A. Tobery ◽  
Michael W. West ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Bacillus Anthracis ◽  
Human Monocyte ◽  
Interleukin 4 ◽  
Human Monocytes ◽  
Content Type ◽  
Bacterial Surface ◽  
Surface Marker Expression ◽  
Immature Dendritic Cells ◽  
The Impact

ABSTRACTThe antiphagocytic capsule ofBacillus anthracisis a major virulence factor. We hypothesized that it may also mediate virulence through inhibition of the host's immune responses. During an infection, the capsule exists attached to the bacterial surface but also free in the host tissues. We sought to examine the impact of free capsule by assessing its effects on human monocytes and immature dendritic cells (iDCs). Human monocytes were differentiated into iDCs by interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) over 7 days in the presence of capsule derived from wild-type encapsulatedB. anthracisAmes (WT) or a control preparation from an isogenicB. anthracisAmes strain that produces only 2% of the capsule of the WT (capAmutant). WT capsule consistently induced release of IL-8 and IL-6 while thecapAmutant control preparation elicited either no response or only a minimal release of IL-8. iDCs that were differentiated in the presence of WT capsule had increased side scatter (SSC), a measure of cellular complexity, when assessed by flow cytometry. iDCs differentiated in the presence of WT capsule also matured less well in response to subsequentB. anthracispeptidoglycan (Ba PGN) exposure, with reduced upregulation of the chemokine receptor CCR7, reduced CCR7-dependent chemotaxis, and reduced release of certain cytokines. Exposure of naive differentiated control iDCs to WT capsule did not alter cell surface marker expression but did elicit IL-8. These results indicate that free capsule may contribute to the pathogenesis of anthrax by suppressing the responses of immune cells and interfering with the maturation of iDCs.

scholarly journals Candida albicans Yeast and Germ Tube Forms Interfere Differently with Human Monocyte Differentiation into Dendritic Cells: a Novel Dimorphism-Dependent Mechanism To Escape the Host's Immune Response

2004 ◽  
Vol 72 (2) ◽  
pp. 833-843 ◽  
Author(s):  
Antonella Torosantucci ◽  
Giulia Romagnoli ◽  
Paola Chiani ◽  
Annarita Stringaro ◽  
Pasqualina Crateri ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Candida Albicans ◽  
Germ Tube ◽  
Immune Surveillance ◽  
Human Monocyte ◽  
Interleukin 4 ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Mrna Transcripts

ABSTRACT The ability of Candida albicans to convert from the yeast (Y) form to mycelial forms through germ tube (GT) formation is considered a key feature of the transition of the organism from commensalism to virulence. We show here that human monocytes cultured with granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) after phagocytosis of Y forms did not differentiate into dendritic cells (DCs); they retained CD14, did not acquire CD1a, and were unable to express the maturation markers CD83 and CCR7. Moreover, they did not produce IL-12p70 but secreted IL-10. In addition, they spontaneously expressed high levels of tumor necrosis factor alpha (TNF-α), IL-6, and IL-8 mRNA transcripts and were able to induce proliferation of alloreactive memory but not naïve T lymphocytes. Conversely, monocytes that had phagocytosed GT forms differentiated into mature CD83+ and CCR7+ DCs; however, there was no up-regulation of CD40, CD80, and major histocompatibility complex class II, irrespective of lipopolysaccharide (LPS) treatment. In addition, these cells were unable to produce IL-12 even after LPS stimulation, but they were not functionally exhausted, as shown by their capacity to express TNF-α and IL-8 mRNA transcripts. These cells were able to prime naïve T cells but not to induce their functional polarization into effector cells. These data indicate that phagocytosis of Y and GT forms has profound and distinct effects on the differentiation pathway of monocytes. Thus, the differentiation of human monocytes into DCs appears to be tunable and exploitable by C. albicans to elude immune surveillance.

scholarly journals Bordetella pertussis Proteins Dominating the Major Histocompatibility Complex Class II-Presented Epitope Repertoire in Human Monocyte-Derived Dendritic Cells

2014 ◽  
Vol 21 (5) ◽  
pp. 641-650 ◽  
Author(s):  
Rachel M. Stenger ◽  
Hugo D. Meiring ◽  
Betsy Kuipers ◽  
Martien Poelen ◽  
Jacqueline A. M. van Gaans-van den Brink ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Bordetella Pertussis ◽  
Human Monocyte ◽  
Class Ii ◽  
T Cell Epitopes ◽  
Major Histocompatibility ◽  
Content Type ◽  
Histocompatibility Complex

ABSTRACTKnowledge of naturally processedBordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presentedB. pertussisCD4+T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4+T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the naturalB. pertussisepitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition ofB. pertussis. A more complete understanding of hallmarks inB. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies.

scholarly journals Enterococcus faecalis Induces Differentiation of Immune-Aberrant Dendritic Cells from Murine Bone Marrow-Derived Stem Cells

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Mohamed Mohamed Elashiry ◽  
Mahmoud Elashiry ◽  
Rana Zeitoun ◽  
Ranya Elsayed ◽  
Fucong Tian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Dendritic Cells ◽  
Enterococcus Faecalis ◽  
Transforming Growth Factor ◽  
Interleukin 4 ◽  
Dependent Manner ◽  
Immune Functions ◽  
Content Type ◽  
Murine Bone Marrow

ABSTRACT Enterococcus faecalis, long implicated in serious systemic infections and failure of root canal treatment, is a persistent inhabitant of oral periapical lesions. Dendritic cells (DCs) and other innate immune cells patrol the oral mucosa for infecting microbes. Dendritic cells are efficient at capturing microbes when immature, whereupon they can transform into potent antigen-presenting cells upon full maturation. Autophagy, a sophisticated intracellular process first described for elimination of damaged organelles, regulates DC maturation and other important immune functions of DCs. The present study examined how E. faecalis influences the differentiation of murine bone marrow-derived stem cells (BMSCs) into functional DCs in the presence of the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Although the viability and differentiation of DCs were not affected by E. faecalis, expression of the autophagy-related proteins ATG7, Beclin1, and LC3bI/II were significantly suppressed in an mTOR-dependent manner. Ultrastructurally, E. faecalis was identified in single-membrane vacuoles, some of which were in the process of binary fission. Bacterium-containing autophagosomes were absent within the cytoplasm. Accessory molecules (major histocompatibility complex class II [MHC-II], CD80, and CD86) and anti-inflammatory cytokine (transforming growth factor β1 [TGF-β1]) were suppressed in E. faecalis-induced DCs, while IL-1β, tumor necrosis factor alpha (TNF-α), and IL-12 levels were upregulated. When pulsed with ovalbumin (OVA), the E. faecalis-induced DCs showed reduction in CD4+ OVA-specific OT-II T cell proliferation. It is concluded that E. faecalis promotes the differentiation of bone marrow stem cells into CD11c-positive DCs with aberrant immune functions while retaining the capability of proinflammatory cytokine induction.

scholarly journals Impact of Gold Nanoparticles on the Functions of Macrophages and Dendritic Cells

2020 ◽  
Author(s):  
Arindam K Dey ◽  
Alexis Gonon ◽  
Eve Isabelle Pécheur ◽  
Mylène Pezet ◽  
Christian Villiers ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Dendritic Cells ◽  
Immune System ◽  
Metabolic Activity ◽  
Immune Cells ◽  
Cell Activation ◽  
Interleukin 4 ◽  
No Production ◽  
Phagocytic Capacity ◽  
The Impact

Abstract Background:Gold nanoparticles (AuNPs) have demonstrated outstanding performance in various biomedical applications, but their effects on the immune system remain ill-defined. We studied the impact of AuNPs on antigen-presenting cells (APCs) because of their phagocytic capacity that allows the accumulation of exogenous materials. As models, we used primary macrophages (M) and dendritic cells (DCs) originating from the bone marrow and tested the modulation of their functions, including phagocytosis, cell activation, production of cytokines and mediators and metabolic activity.Results: The AuNPs by themselves displayed no significant effect on M and DCs functions. However, when exposed to AuNPs, M and DCs responded differently to lipopolysaccharide (LPS) or Interleukin- 4(IL-4) stimulations. We showed AuNPs altered cytokine and reactive oxygen species (ROS) productions differently in M and DCs, whereas nitric oxide (NO) production by both cells remained unaffected. The metabolic profile underpins all functions of the immune cells and their polarisation. The analysis of the metabolic activity revealed that AuNPs significantly altered mitochondrial respiration and glycolysis of M, while only little effect was seen on DCs. Furthermore, we showed that T cell responses increased when antigen was presented by AuNPs-exposed DCs, leading to stronger Th1, Th2, and Th17 responses. Conclusions: Our data provide new insights into the complexity of the effects of AuNPs on the immune system. Although AuNPs may be considered on the whole to be devoid of direct significant effect, they may induce discrete modifications on some functions that can differ among the immune cells.

scholarly journals Bacillus anthracis SlaQ Promotes S-Layer Protein Assembly

2015 ◽  
Vol 197 (19) ◽  
pp. 3216-3227 ◽  
Author(s):  
Sao-Mai Nguyen-Mau ◽  
So-Young Oh ◽  
Daphne I. Schneewind ◽  
Dominique Missiakas ◽  
Olaf Schneewind
Keyword(s):  
Bacillus Anthracis ◽  
Self Assembly ◽  
Protein Assembly ◽  
Crystalline Lattice ◽  
Cell Wall Polysaccharide ◽  
Cytoplasmic Protein ◽  
Content Type ◽  
Bacterial Surface

ABSTRACTBacillus anthracisvegetative forms assemble an S-layer comprised of two S-layer proteins, Sap and EA1. A hallmark of S-layer proteins are their C-terminal crystallization domains, which assemble into a crystalline lattice once these polypeptides are deposited on the bacterial surface via association between their N-terminal S-layer homology domains and the secondary cell wall polysaccharide. Here we show thatslaQ, encoding a small cytoplasmic protein conserved among pathogenic bacilli elaborating S-layers, is required for the efficient secretion and assembly of Sap and EA1. S-layer protein precursors cosediment with SlaQ, and SlaQ appears to facilitate Sap assembly. Purified SlaQ polymerizes and when mixed with purified Sap promotes thein vitroformation of tubular S-layer structures. A model is discussed whereby SlaQ, in conjunction with S-layer secretion factors SecA2 and SlaP, promotes localized secretion and S-layer assembly inB. anthracis.IMPORTANCES-layer proteins are endowed with the propensity for self-assembly into crystalline arrays. Factors promoting S-layer protein assembly have heretofore not been reported. We identifiedBacillus anthracisSlaQ, a small cytoplasmic protein that facilitates S-layer protein assemblyin vivoandin vitro.

scholarly journals Bordetella pertussis Naturally Occurring Isolates with Altered Lipooligosaccharide Structure Fail To Fully Mature Human Dendritic Cells

2014 ◽  
Vol 83 (1) ◽  
pp. 227-238 ◽  
Author(s):  
Jolanda Brummelman ◽  
Rosanne E. Veerman ◽  
Hendrik Jan Hamstra ◽  
Anna J. M. Deuss ◽  
Tim J. Schuijt ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Bordetella Pertussis ◽  
Lipid A ◽  
Whooping Cough ◽  
Human Monocyte ◽  
Innate Immune ◽  
Clinical Isolates ◽  
Immune Recognition ◽  
Content Type

Bordetella pertussisis a Gram-negative bacterium and the causative agent of whooping cough. Despite high vaccination coverage, outbreaks are being increasingly reported worldwide. Possible explanations include adaptation of this pathogen, which may interfere with recognition by the innate immune system. Here, we describe innate immune recognition and responses to differentB. pertussisclinical isolates. By using HEK-Blue cells transfected with different pattern recognition receptors, we found that 3 out of 19 clinical isolates failed to activate Toll-like receptor 4 (TLR4). These findings were confirmed by using the monocytic MM6 cell line. Although incubation with high concentrations of these 3 strains resulted in significant activation of the MM6 cells, it was found to occur mainly through interaction with TLR2 and not through TLR4. When using live bacteria, these 3 strains also failed to activate TLR4 on HEK-Blue cells, and activation of MM6 cells or human monocyte-derived dendritic cells was significantly lower than activation induced by the other 16 strains. Mass spectrum analysis of the lipid A moieties from these 3 strains indicated an altered structure of this molecule. Gene sequence analysis revealed mutations in genes involved in lipid A synthesis. Findings from this study indicate thatB. pertussisisolates that do not activate TLR4 occur naturally and that this phenotype may give this bacterium an advantage in tempering the innate immune response and establishing infection. Knowledge on the strategies used by this pathogen in evading the host immune response is essential for the improvement of current vaccines or for the development of new ones.

Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus

Microbiology ◽  
2000 ◽  
Vol 81 (2) ◽  
pp. 393-399 ◽  
Author(s):  
S. Riegler ◽  
H. Hebart ◽  
H. Einsele ◽  
P. Brossart ◽  
G. Jahn ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Human Cytomegalovirus ◽  
Growth Curves ◽  
Antigen Expression ◽  
Single Step ◽  
Productive Infection ◽  
Interleukin 4 ◽  
Progeny Virus ◽  
Blood Monocytes ◽  
Immature Dendritic Cells

The susceptibility of monocyte-derived immature dendritic cells (DC) to infection by various strains of human cytomegalovirus (HCMV) was analysed. Immature DC were generated by incubation of peripheral blood monocytes with interleukin-4 and granulocyte–macrophage colony-stimulating factor for 7 days and were characterized by a CD1a+/CD40+/CD80+/CD86+/HLA-DR+/CD14− phenotype. Viral antigen expression and production of infectious progeny virus were analysed in infected immature DC cultures. Immature DC were 80–90 % susceptible to HCMV strains that had been propagated in endothelial cell culture, whereas the infection rate was negligible with fibroblast-adapted HCMV strains. Immature DC infection resulted in expression of viral immediate early, early and late genes. Productive infection was proven by the detection of infectious virus in single-step growth curves and in infectious centre assays. It is concluded that HCMV might interfere with the host immune reaction by permissive, lytic infection of immature DC.

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