scholarly journals Interaction of Neisseria meningitidis with Human Dendritic Cells

2001 ◽  
Vol 69 (11) ◽  
pp. 6912-6922 ◽  
Author(s):  
Annette Kolb-Mäurer ◽  
Alexandra Unkmeir ◽  
Ulrike Kämmerer ◽  
Claudia Hübner ◽  
Thomas Leimbach ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Neisseria Meningitidis ◽  
Proinflammatory Cytokines ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Factor Alpha ◽  
Human Dendritic Cells ◽  
Necrosis Factor

ABSTRACT Infection with Neisseria meningitidis serogroup B is responsible for fatal septicemia and meningococcal meningitis. The severity of disease directly correlates with the production of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these cytokines has not been clearly defined yet. Since bacterial infection involves the activation of dendritic cells (DCs), we analyzed the interaction of N. meningitidis with monocyte-derived DCs. Using N. meningitidis serogroup B wild-type and unencapsulated bacteria, we found that capsule expression significantly impaired neisserial adherence to DCs. In addition, phagocytic killing of the bacteria in the phagosome is reduced by at least 10- to 100-fold. However, all strains induced strong secretion of proinflammatory cytokines TNF-α, IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h postinfection [p.i.]), with significantly increased cytokine levels being measurable by as early as 6 h p.i. Levels of IL-1β, in contrast, were increased only 200- to 400-fold at 20 h p.i. with barely measurable induction at 6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free supernatants of Neisseria cultures containing neisserial lipooligosaccharide as the main factor. Our data suggest that activated DCs may be a significant source of high levels of proinflammatory cytokines in neisserial infection and thereby may contribute to the pathology of meningococcal disease.

scholarly journals Lipooligosaccharide and Polysaccharide Capsule: Virulence Factors of Neisseria meningitidis That Determine Meningococcal Interaction with Human Dendritic Cells

2002 ◽  
Vol 70 (5) ◽  
pp. 2454-2462 ◽  
Author(s):  
Alexandra Unkmeir ◽  
Ulrike Kämmerer ◽  
Anne Stade ◽  
Claudia Hübner ◽  
Sabine Haller ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Neisseria Meningitidis ◽  
Wild Type ◽  
Proinflammatory Response ◽  
Necrosis Factor Alpha ◽  
Cytokine Induction ◽  
Cytokines And Chemokines ◽  
Factor Alpha ◽  
Human Dendritic Cells ◽  
Necrosis Factor

ABSTRACT In this work we analyzed the roles of meningococcal lipooligosaccharide (LOS) and capsule expression in the interaction of Neisseria meningitidis with human dendritic cells (DC). Infection of DC with serogroup B wild-type meningococci induced a strong burst of the proinflammatory cytokines and chemokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. In contrast, a serogroup B mutant strain lacking LOS expression barely led to cytokine induction, demonstrating that meningococcal LOS is the main mediator of the proinflammatory response in human DC. Sialylation of meningococcal LOS did not influence cytokine secretion by DC. However, we found the phagocytosis of N. meningitidis by human DC to be inhibited by LOS sialylation. In addition, the expression of the meningococcal serogroup A, B, and C capsules dramatically reduced DC adherence of N. meningitidis and phagocytosis to some extent. Hence, LOS sialylation and capsule expression are independent mechanisms protecting N. meningitidis from the phagocytic activity of human DC.

scholarly journals Maturation of Human Dendritic Cells by Cell Wall Skeleton of Mycobacterium bovis Bacillus Calmette-Guérin: Involvement of Toll-Like Receptors

2000 ◽  
Vol 68 (12) ◽  
pp. 6883-6890 ◽  
Author(s):  
Shoutaro Tsuji ◽  
Misako Matsumoto ◽  
Osamu Takeuchi ◽  
Shizuo Akira ◽  
Ichiro Azuma ◽  
...  
Keyword(s):  
Cell Wall ◽  
Dendritic Cells ◽  
Mycobacterium Bovis ◽  
Surface Expression ◽  
Necrosis Factor Alpha ◽  
Mycolic Acids ◽  
Tnf Α ◽  
Toll Like Receptor 2 ◽  
Factor Alpha ◽  
Human Dendritic Cells

ABSTRACT The constituents of mycobacteria are an effective immune adjuvant, as observed with complete Freund's adjuvant. In this study, we demonstrated that the cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guérin (BCG-CWS), a purified noninfectious material consisting of peptidoglycan, arabinogalactan, and mycolic acids, induces maturation of human dendritic cells (DC). Surface expression of CD40, CD80, CD83, and CD86 was increased by BCG-CWS on human immature DC, and the effect was similar to those of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), heat-killed BCG, and viable BCG. BCG-CWS induced the secretion of TNF-α, IL-6, and IL-12 p40. CD83 expression was increased by a soluble factor secreted from BCG-CWS-treated DC and was completely inhibited by monoclonal antibodies against TNF-α. BCG-CWS-treated DC stimulated extensive allogeneic mixed lymphocyte reactions. The level of TNF-α secreted through BCG-CWS was partially suppressed in murine macrophages with no Toll-like receptor 2 (TLR 2) or TLR4 and was completely lost in TLR2 and TLR4 double-deficient macrophages. These results suggest that the BCG-CWS induces TNF-α secretion from DC via TLR2 and TLR4 and that the secreted TNF-α induces the maturation of DC per se.

scholarly journals Transient Neutralization of Tumor Necrosis Factor Alpha Can Produce a Chronic Fungal Infection in an Immunocompetent Host: Potential Role of Immature Dendritic Cells

2005 ◽  
Vol 73 (1) ◽  
pp. 39-49 ◽  
Author(s):  
Amy C. Herring ◽  
Nicole R. Falkowski ◽  
Gwo-Hsiao Chen ◽  
Rod A. McDonald ◽  
Galen B. Toews ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Fungal Infection ◽  
Immune Deviation ◽  
Immunocompetent Host ◽  
Necrosis Factor Alpha ◽  
Immature Dendritic Cells ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT The mechanisms underlying induction of immune dysregulation and chronic fungal infection by a transient tumor necrosis factor alpha (TNF-α) deficiency remain to be defined. The objective of our studies was to determine the potential contribution of neutropenia and immature dendritic cells to the immune deviation. Administration of an anti-TNF-α monoclonal antibody at day 0 neutralized TNF-α only during the first week of a pulmonary Cryptococcus neoformans infection. Transient neutralization of TNF-α resulted in transient depression of interleukin-12 (IL-12), monocyte chemotactic protein 1 (MCP-1), and gamma interferon (IFN-γ) production but permanently impaired long-term clearance of the infection from the lungs even after the levels of these cytokines increased and a vigorous inflammatory response developed. Early neutrophil recruitment was defective in the absence of TNF-α. However, as demonstrated by neutrophil depletion studies, this did not account for the decrease in IL-12 and IFN-γ levels and did not play a role in establishing chronic pulmonary cryptococcal infection. Transient TNF-α neutralization also produced a deficiency in CD11c+ MHC II+ cells and IL-12 in the lymph nodes, potentially implicating a defect in mature dendritic cell trafficking. Transfer of cryptococcal antigen-pulsed immature dendritic cells into naïve mice prior to intratracheal challenge resulted in the development of a nonprotective immune response to C. neoformans that was similar to that observed in anti-TNF-α-treated mice (increased IL-4, IL-5, and IL-10 levels, pulmonary eosinophilia, and decreased clearance). Thus, stimulation of an antifungal response by immature dendritic cells can result in an immune deviation similar to that produced by transient TNF-α deficiency, identifying a new mechanism by which a chronic fungal infection can occur in an immunocompetent host.

scholarly journals NK Cells Mediate Increase of Phagocytic Activity but Not of Proinflammatory Cytokine (Interleukin-6 [IL-6], Tumor Necrosis Factor Alpha, and IL-12) Production Elicited in Splenic Macrophages by Tilorone Treatment of Mice during Acute Systemic Candidiasis

2002 ◽  
Vol 9 (6) ◽  
pp. 1282-1294 ◽  
Author(s):  
José Juan Gaforio ◽  
Elena Ortega ◽  
Ignacio Algarra ◽  
María José Serrano ◽  
Gerardo Alvarez de Cienfuegos
Keyword(s):  
Nk Cells ◽  
Mhc Class Ii ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Systemic Candidiasis ◽  
Necrosis Factor Alpha ◽  
Splenic Macrophages ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The participation of NK cells in the activation of splenic macrophages or in resistance to systemic candidiasis is still a matter of debate. We had previously reported that there is a correlation between natural killer cell activation and resistance to systemic candidiasis. In those experiments we had used tilorone to boost NK cell activity in mice. Here we show a mechanism elicited by tilorone in splenic macrophages which could explain their effect on mouse survival during acute disseminated Candida albicans infection. The results demonstrate that tilorone treatment elicits, by a direct effect, the production of proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α], and IL-12) by splenic macrophages. In addition, it increases the capacity of splenic macrophages to phagocytize C. albicans through activation of NK cells. We also demonstrate that the presence of NK cells is essential for maintaining a basal level of phagocytic activity, which characterizes splenic macrophages of naïve control mice. The results demonstrate that it is possible to identify two phenotypically and functionally peculiar cell populations among splenic macrophages: (i) cells of the “stimulator/secretor phenotype,” which show high levels of major histocompatibility complex (MHC) class II surface expression, are poorly phagocytic, and synthesize the proinflammatory cytokines IL-6, TNF-α, and IL-12, and (ii) cells of the “phagocytic phenotype,” which express low levels of MHC class II molecules, are highly phagocytic, and do not secrete proinflammatory cytokines.

scholarly journals Tumor Necrosis Factor Alpha Transcription in Macrophages Is Attenuated by an Autocrine Factor That Preferentially Induces NF-κB p50

1998 ◽  
Vol 18 (10) ◽  
pp. 5678-5689 ◽  
Author(s):  
Mark Baer ◽  
Allan Dillner ◽  
Richard C. Schwartz ◽  
Constance Sedon ◽  
Sergei Nedospasov ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Proinflammatory Cytokines ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Tumor Cell Line ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Macrophages are a major source of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), which are expressed during conditions of inflammation, infection, or injury. We identified an activity secreted by a macrophage tumor cell line that negatively regulates bacterial lipopolysaccharide (LPS)-induced expression of TNF-α. This activity, termed TNF-α-inhibiting factor (TIF), suppressed the induction of TNF-α expression in macrophages, whereas induction of three other proinflammatory cytokines (interleukin-1β [IL-1β], IL-6, and monocyte chemoattractant protein 1) was accelerated or enhanced. A similar or identical inhibitory activity was secreted by IC-21 macrophages following LPS stimulation. Inhibition of TNF-α expression by macrophage conditioned medium was associated with selective induction of the NF-κB p50 subunit. Hyperinduction of p50 occurred with delayed kinetics in LPS-stimulated macrophages but not in fibroblasts. Overexpression of p50 blocked LPS-induced transcription from a TNF-α promoter reporter construct, showing that this transcription factor is an inhibitor of the TNF-α gene. Repression of the TNF-α promoter by TIF required a distal region that includes three NF-κB binding sites with preferential affinity for p50 homodimers. Thus, the selective repression of the TNF-α promoter by TIF may be explained by the specific binding of inhibitory p50 homodimers. We propose that TIF serves as a negative autocrine signal to attenuate TNF-α expression in activated macrophages. TIF is distinct from the known TNF-α-inhibiting factors IL-4, IL-10, and transforming growth factor β and may represent a novel cytokine.

scholarly journals DYNAMICS OF CYTOKINS AND THEIR INTERRELATION IN LIVER CIRRHOSIS

2015 ◽  
Vol 7 (1) ◽  
pp. 110-114
Author(s):  
B B Fishman ◽  
M A Toneeva ◽  
V E Kulikov ◽  
V A Kornilova ◽  
E R Antonova
Keyword(s):  
Liver Cirrhosis ◽  
Reference Values ◽  
Average Concentration ◽  
Necrosis Factor Alpha ◽  
Class A ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Class B ◽  
Factor Alpha ◽  
Necrosis Factor

The research objectives are to determine serum interleukins (IL-2, IL-6) and tumor necrosis factor alpha (TNF - α) and evaluate their interrelation in liver cirrhosis (class A, B, C according to Chad - Pugh). 117 patients were examined and their cytokines levels were determined using enzyme-linked immunosorbent assay.Elevation of cytokine levels IL-2, I-6 and TNF-α within reference values was found in liver cirrhosis cases, expect for level IL-6 in liver cirrhosis cases of class C. In these cases IL-6 level exceeds reference values and is within the limit of 9,94 - 25,21 pg / ml with average concentration of 14,89±4,96 pg / ml. Correlation is found between TNF- α and IL-6 (r = - 0,499) in liver cirrhosis of class A and correlation between TNF- α and IL-2 (r = 0,421) is found in liver cirrhosis of class B.

Triterpenoid CDDO-IM protects against lipopolysaccharide-induced inflammatory response and cytotoxicity in macrophages: The involvement of the NF-κB signaling pathway

2022 ◽  
pp. 153537022110669
Author(s):  
Hassan Ahmed ◽  
Urooj Amin ◽  
Xiaolun Sun ◽  
Demetrius R Pitts ◽  
Yunbo Li ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Cytokine ◽  
Interleukin 1 ◽  
Severe Form ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Factor Alpha ◽  
Gene Expression Levels

Lipopolysaccharide (LPS), also known as endotoxin, can trigger septic shock, a severe form of inflammation-mediated sepsis with a very high mortality rate. However, the precise mechanisms underlying this endotoxin remain to be defined and detoxification of LPS is yet to be established. Macrophages, a type of immune cells, initiate a key response responsible for the cascade of events leading to the surge in inflammatory cytokines and immunopathology of septic shock. This study was undertaken to determine whether the LPS-induced inflammation in macrophage cells could be ameliorated via CDDO-IM (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a novel triterpenoid compound. Data from this study show that gene expression levels of inflammatory cytokine genes such as interleukin-1 beta (IL-1β), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) were considerably increased by treatment with LPS in macrophages differentiated from ML-1 monocytes. Interestingly, LPS-induced increase in expression of pro-inflammatory cytokine levels is reduced by CDDO-IM. In addition, endogenous upregulation of a series of antioxidant molecules by CDDO-IM provided protection against LPS-induced cytotoxicity in macrophages. LPS-mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) transcriptional activity was also noted to decrease upon treatment with CDDO-IM in macrophages suggesting the involvement of the NF-κB signaling. This study would contribute to improve our understanding of the detoxification of endotoxin LPS by the triterpenoid CDDO-IM.

scholarly journals Immunomodulating Properties of the Antibiotic Novobiocin in Human Monocytes

1998 ◽  
Vol 42 (8) ◽  
pp. 1911-1916 ◽  
Author(s):  
Anja Lührmann ◽  
Jürgen Thölke ◽  
Ingrid Behn ◽  
Jens Schumann ◽  
Gisa Tiegs ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Adp Ribosylation ◽  
Surface Molecules ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT We show that the coumeromycin antibiotic novobiocin, a potent inhibitor of ADP ribosylation, prevents lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-10 secretion in human peripheral blood mononuclear cells. It shares these cytokine-suppressing properties with other inhibitors of ADP ribosylation. We found that novobiocin prevents TNF-α production by inhibiting translation of the TNF-α mRNA. Elevated TNF-α levels in mice treated withd-galactosamine (GalN)-LPS or GalN-TNF were not reduced by novobiocin; however, the drug exhibited hepatoprotective properties. Novobiocin causes downregulation of the surface molecules on monocytes, among which CD14 was the most affected. The diminished expression of surface molecules was not observed on T and B lymphocytes. Similar to other inhibitors of ADP ribosylation, novobiocin prevents LPS-induced phosphate labelling of γ-actins.

scholarly journals Haemophilus ducreyi Lipooligosaccharides Induce Expression of the Immunosuppressive Enzyme Indoleamine 2,3-Dioxygenase via Type I Interferons and Tumor Necrosis Factor Alpha in Human Dendritic Cells

2011 ◽  
Vol 79 (8) ◽  
pp. 3338-3347 ◽  
Author(s):  
Wei Li ◽  
Barry P. Katz ◽  
Stanley M. Spinola
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis ◽  
Treg Cells ◽  
Type I Interferons ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTHaemophilus ducreyicauses chancroid, a genital ulcer disease. In human inoculation experiments, most volunteers fail to clear the bacteria despite the infiltration of innate and adaptive immune cells to the infected sites. The immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in thel-tryptophan-kynurenine metabolic pathway. Tryptophan depletion and tryptophan metabolites contribute to pathogen persistence by inhibiting T cell proliferation, inducing T cell apoptosis, and promoting the expansion of FOXP3+regulatory T (Treg) cells. We previously found that FOXP3+Treg cells are enriched in experimental lesions and thatH. ducreyiinduced IDO transcription in dendritic cells (DC) derived from blood of infected volunteers who developed pustules. Here, we showed that enzymatically active IDO was induced in DC byH. ducreyi. Neutralizing antibodies against interferon alpha/beta receptor 2 chain (IFNAR2) and tumor necrosis factor alpha (TNF-α) inhibited IDO induction. Inhibitors of the mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) also inhibited IDO expression. Neither bacterial contact with nor uptake by DC was required for IDO activation.H. ducreyiculture supernatant andH. ducreyilipooligosaccharides (LOS) induced IDO expression, which required type I interferons, TNF-α, and the three MAPK (p38, c-Jun N-terminal kinase, and extracellular signal regulated kinase) and NF-κB pathways. In addition, LOS-induced IFN-β activated the JAK-STAT pathway. Blocking the LOS/Toll-like receptor 4 (TLR4) signaling pathway greatly reducedH. ducreyi-induced IDO production. These findings indicate thatH. ducreyi-induced IDO expression in DC is largely mediated by LOS via type I interferon- and TNF-α-dependent mechanisms and the MAPK, NF-κB, and JAK-STAT pathways.

scholarly journals Suppression of Macrophage Activation with CNI-1493 Increases Survival in Infant Rats with Systemic Haemophilus influenzae Infection

2000 ◽  
Vol 68 (9) ◽  
pp. 5329-5334 ◽  
Author(s):  
Carl Granert ◽  
Hana Abdalla ◽  
Lars Lindquist ◽  
Asim Diab ◽  
Moiz Bakhiet ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Infant Rats ◽  
Cytokine Inhibition ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
The Brain ◽  
Necrosis Factor

ABSTRACT CNI-1493, a potent macrophage deactivator, was used to treat infant rats systemically infected with Haemophilus influenzae type b (Hib). CNI-1493 was injected 1 h prior to bacterial inoculation and 24 h later and resulted in a 75 percent increased rate of survival compared to that for untreated controls. The effect of CNI-1493 on the inflammatory response was studied by immunohistochemical detection of individual tumor necrosis factor alpha (TNF-α)-, interleukin 1 beta (IL-1β)-, and gamma interferon (IFN-γ)-producing cells in the spleen. A significant reduction of the incidence of TNF-α- and IL-1β-expressing cells was found for CNI-1493-treated animals. IFN-γ expression was not suppressed by CNI-1493, indicating that cytokine inhibition was specific in macrophages. CNI-1493 significantly reduced the number of infiltrating granulocytes in the brain from that for controls. This study provides evidence that CNI-1493 protects against lethal Hib infection by deactivating the inflammatory cascade in infant rats.

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