scholarly journals A Mutant of Staphylococcal Enterotoxin C Devoid of Bacterial Superantigenic Activity Elicits a Th2 Immune Response for Protection against Staphylococcus aureus Infection

2005 ◽  
Vol 73 (1) ◽  
pp. 174-180 ◽  
Author(s):  
Dong-Liang Hu ◽  
Jing-Chun Cui ◽  
Katsuhiko Omoe ◽  
Hiroshi Sashinami ◽  
Yuichi Yokomizo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Neutralizing Antibodies ◽  
Interleukin 10 ◽  
Staphylococcal Enterotoxin ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
T Helper 2 ◽  
Th2 Immune Response ◽  
Ifn Γ

ABSTRACT Staphylococcal enterotoxin C (SEC), a bacterial superantigenic exotoxin, is commonly produced by invasive Staphylococcus aureus isolates, especially methicillin-resistant strains and isolates from animal diseases. We constructed and expressed a nontoxic mutant SEC (mSEC) and investigated whether immunization with mSEC, which is devoid of superantigenic activity, can protect against S. aureus infection. Mice were immunized with mSEC and challenged with viable S. aureus. The bacterial counts in the organs of mSEC-immunized mice were significantly lower and the survival rate was higher than the corresponding values for the control group. Immunization with mSEC strongly induced the production of T-helper 2 type antibodies, immunoglobulin G1, and immunoglobulin G2b. The production of interleukin-10 (IL-10) and IL-4 was significantly greater in immunized mice challenged with S. aureus than in the control mice, whereas the production of gamma interferon (IFN-γ) was significantly decreased in the immunized mice. The cytokine response in a spleen cell culture that was stimulated with heat-killed S. aureus or SEC showed that immunization with mSEC inhibited IFN-γ production and up-regulated IL-10 production in vitro. Furthermore, IFN-γ and tumor necrosis factor alpha production in vitro was significantly inhibited by sera from mSEC-immunized mice but not by sera from control mice. These results suggest that immunization with mSEC devoid of superantigenic properties provides protection against S. aureus infection and that the protection might be mediated by SEC-specific neutralizing antibodies.

dSLIM Immunomodulators Induce Anti-Tumor Responses Both In Vitro and In Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1727-1727
Author(s):  
Manuel Schmidt ◽  
Javier de Cristobal ◽  
Astrid Sander ◽  
Bernadette Brzezicha ◽  
Sven A. König Merediz ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
De Novo ◽  
Tumor Cell Line ◽  
Control Group ◽  
Γδt Cells ◽  
Ifn Γ

Abstract Cytosine-guanine (CpG) motifs containing oligonucleotides (ODN) are commonly used for immunomodulatory purpose in cancer therapy and for the treatment of allergic diseases since they resemble bacterial DNA and serve as “danger signals”. These CpG-ODNs promote predominately a TH1-response with secretion of IL-12 and IFN-γ, In addition their broad potential includes activation of B-cell proliferation, monocyte stimulation and secretion of IgM and IL-6, and stimulation of plasmacytoid DC to produce IFN-α/-β and thus γδT-cells and NK-cells to express CD69 and secrete IFN-γ. Usually phosphorothioate (PS) modifications are to enhance the stability, but these are leading to several side-effects, like severe organ enlargements, morphological changes and immunosuppression in mice. We designed immunomodulatory molecules based on short covalently-closed dumbbell-like structures (dSLIM) to stabilize the DNA without the otherwise necessary PS-modification. To evaluate the anti-tumor effect of the dSLIM molecules we developed an in vitro anti-tumor assay. This assay uses supernatant from dSLIM-activated human PBMCs for incubation with tumor cells in vitro. We observed increased apoptosis and necrosis of the HT-29 tumor cell line after incubation with supernatant from dSLIM-treated PBMC which was significantly higher than the effect of supernatant from non-treated PBMC. In addition, supernatant from dSLIM-treated PBMC increased the expression of HLA-ABC on the tumor cells, a pre-requisite for tumor cell recognition by the immune system. These effects were confirmed with human HEK293 and murine Renca cell lines. Analyzing the effect with neutralizing antibodies to various apoptosis-related cytokines, we observed a crucial role of IFN-γ but not IFN-α or TNFα. To investigate the anti-tumor effects of dSLIM in vivo, we employed a SKH1 murine model which is prone to spontaneous development of papillomas. Using chemicals for initiation and weekly promotion of de novo papilloma development we compared groups of weekly s.c. or i.p. dSLIM injections, respectively, with the PBS control group. The number of papilloma developing mice was significantly lower in the dSLIM groups and the total number of papillomas on all mice was reduced by approximately 50%. In conclusion, we showed that dSLIM immunomodulators exhibit potent anti-tumor effects in vitro and in vivo.

scholarly journals Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response to Leishmania amazonensis in Healthy Volunteers

2001 ◽  
Vol 69 (12) ◽  
pp. 7453-7460 ◽  
Author(s):  
M. M. L. Pompeu ◽  
C. Brodskyn ◽  
M. J. Teixeira ◽  
J. Clarêncio ◽  
J. Van Weyenberg ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Leishmania Amazonensis ◽  
Cell Mediated Immunity ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT The initial encounter of Leishmania cells and cells from the immune system is fundamentally important in the outcome of infection and determines disease development or resistance. We evaluated the anti-Leishmania amazonensis response of naive volunteers by using an in vitro priming (IVP) system and comparing the responses following in vivo vaccination against the same parasite. In vitro stimulation allowed us to distinguish two groups of individuals, those who produced small amounts of gamma interferon (IFN-γ) (n = 16) (low producers) and those who produced large amounts of this cytokine (n = 16) (high producers). IFN-γ production was proportional to tumor necrosis factor alpha and interleukin 10 (IL-10) levels but did not correlate with IL-5 production. Volunteers who produced small amounts of IFN-γ in vitro remained low producers 40 days after vaccination, whereas high producers exhibited increased IFN-γ production. However, 6 months after vaccination, all individuals tested produced similarly high levels of IFN-γ upon stimulation of their peripheral blood mononuclear cells with Leishmania promastigotes, indicating that low in vitro producers respond slowly in vivo to vaccination. In high IFN-γ producers there was an increased frequency of activated CD8+ T cells both in vitro and in vivo compared to the frequency in low producers, and such cells were positive for IFN-γ as determined by intracellular staining. Such findings suggest that IVP responses can be used to predict the pace of postvaccination responses of test volunteers. Although all vaccinated individuals eventually have a potent anti-Leishmania cell-mediated immunity (CMI) response, a delay in mounting the CMI response may influence resistance against leishmaniasis.

scholarly journals Transfer of Antigen-Pulsed Dendritic Cells Induces Specific T-Cell Proliferation and a Therapeutic Effect against Long-Term Helicobacter pylori Infection in Mice

2006 ◽  
Vol 74 (2) ◽  
pp. 984-993 ◽  
Author(s):  
Satoshi Otsu ◽  
Kazuyo Gotoh ◽  
Tetsu Yamashiro ◽  
Junpei Yamagata ◽  
Kouichirou Shin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Interleukin 10 ◽  
Cell Mediated Immunity ◽  
Mouse Bone Marrow ◽  
Peptic Ulcers ◽  
Th1 Cell ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
H Pylori

ABSTRACT Helicobacter pylori causes persistent infection of the stomach and results in chronic gastritis and peptic ulcers. Jaws II cells, derived from mouse bone marrow, were pulsed with live or formalin-killed or whole-cell sonicates (WCS) of H. pylori. Representative cell surface molecules were expressed at substantial levels on Jaws II cells, indicating that appropriate maturation of the cells was achieved with the three H. pylori antigens without any significant differences. H. pylori WCS-pulsed Jaws II cells secreted a significant amount of tumor necrosis factor alpha into the culture supernatant. The naïve T cells exposed to the WCS-pulsed Jaws II cells showed significant proliferation and gamma interferon (IFN-γ) and interleukin-10 (IL-10) production in vitro. A 2-log reduction in the number of colonizing bacteria was observed in the mice treated with the WCS-pulsed Jaws II cells; however, no significant reductions were achieved in mice treated with Jaws II cells pulsed with other H. pylori antigens. Up-regulated production of IFN-γ and IL-10 was observed in the stomachs of the mice treated with the WCS-pulsed Jaws II cells, which is consistent with the result obtained in vitro. There were no differences in gastritis scores or H. pylori-specific antibody titers among the mice treated with Jaws II cells pulsed with the three different H. pylori antigens. The results suggest that Th1 cell-mediated immunity in combination with Th2 cell-mediated immunity plays a role in reducing colonizing bacterial numbers in mice with chronic H. pylori infections.

dSLIM Immunomodulators Induce Anti-Tumor Responses Both In Vitro and In Vivo.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5527-5527
Author(s):  
Manuel Schmidt ◽  
Javier de Cristobal ◽  
Astrid Sander ◽  
Bernadette Brzezicha ◽  
Sven A. Koenig-Merediz ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
De Novo ◽  
Tumor Cell Line ◽  
Control Group ◽  
Γδt Cells ◽  
Ifn Γ

Abstract Cytosine-guanine (CpG) motifs containing oligonucleotides (ODN) are commonly used for immunomodulatory purpose in cancer therapy and for the treatment of allergic diseases since they resemble bacterial DNA and serve as “danger signals”. These CpG-ODNs promote predominately a TH1-response with secretion of IL-12 and IFN-γ, In addition their broad potential includes activation of B-cell proliferation, monocyte stimulation and secretion of IgM and IL-6, and stimulation of plasmacytoid DC to produce IFN-α/-β and thus γδT-cells and NK-cells to express CD69 and secrete IFN-γ. Usually phosphorothioate (PS) modifications are to enhance the stability, but these are leading to several side-effects, like severe organ enlargements, morphological changes and immunosuppression in mice. We designed immunomodulatory molecules based on short covalently-closed dumbbell-like structures (dSLIM) to stabilize the DNA without the otherwise necessary PS-modification. To evaluate the anti-tumor effect of the dSLIM molecules we developed an in vitro anti-tumor assay. This assay uses supernatant from dSLIM-activated human PBMCs for incubation with tumor cells in vitro. We observed increased apoptosis and necrosis by the HT-29 tumor cell line after incubation with supernatant from dSLIM-treated PBMC which was significantly higher than the effect of supernatant from non-treated PBMC. In addition, supernatant from dSLIM-treated PBMC increased the expression of HLA-ABC on the tumor cells, a pre-requisite for tumor cell recognition by the immune system. These effects were confirmed with human HEK293 and murine Renca cell lines. Analyzing the effect with neutralizing antibodies to various apoptosis-related cytokines, we observed a crucial role of IFN-γ but not IFN-α or TNFα. To investigate the anti-tumor effects of dSLIM in vivo, we employed a SKH1 murine model which is prone to spontaneous development of papillomas. Using chemicals for initiation and weekly promotion of de novo papilloma development we compared groups of weekly s.c. or i.p. dSLIM injections, respectively, with the PBS control group. The number of papilloma developing mice was significantly lower in the dSLIM groups and the total number of papillomas on all mice was reduced by approximately 50%. In conclusion, we showed that dSLIM immunomodulators exhibit potent anti-tumor effects in vitro and in vivo.

scholarly journals Modulation of Cytokine Release in Ex Vivo-Stimulated Blood from Borreliosis Patients

2001 ◽  
Vol 69 (2) ◽  
pp. 687-694 ◽  
Author(s):  
Isabel Diterich ◽  
Luc Härter ◽  
Dieter Hassler ◽  
Albrecht Wendel ◽  
Thomas Hartung
Keyword(s):  
Ex Vivo ◽  
Interleukin 10 ◽  
Cytokine Response ◽  
Healthy Controls ◽  
Cytokine Release ◽  
Necrosis Factor Alpha ◽  
Cell Counts ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT In lipopolysaccharide-stimulated blood from 71 late-stage borreliosis patients, the ex vivo cytokine release capacity of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) was reduced to 28% ± 5% and to 31% ± 5% (P ≤ 0.001), respectively, compared to that of 24 healthy controls. White blood cell counts were normal in both groups. To investigate direct interactions between the pathogen and the immune cells, blood from healthy controls was exposed in vitro to live or heat-killedBorrelia or to Borrelia lysate. Compared to the pattern induced by bacterial endotoxins, a reduced release of TNF-α and IFN-γ and an enhanced secretion of interleukin-10 and granulocyte colony-stimulating factor was found. In blood from 10 borreliosis patients stimulated with Borrelia lysate, TNF-α formation was decreased to 31% ± 14% and IFN-γ formation was decreased to 8% ± 3% (P ≤ 0.001) compared to the cytokine response of blood from healthy controls (n = 24). We propose to consider anti-inflammatory changes in the blood cytokine response capacity elicited by Borrelia as a condition that might favor the persistence of the spirochete.

scholarly journals Effects and Responsiveness of a Multicomponent Intervention on Body Composition, Physical Fitness and Leptin in Overweight/Obese Adolescents

2021 ◽  
Vol 18 (14) ◽  
pp. 7267
Author(s):  
Leticia Borfe ◽  
Caroline Brand ◽  
Letícia Schneiders ◽  
Jorge Mota ◽  
Claudia Cavaglieri ◽  
...  
Keyword(s):  
Body Composition ◽  
Physical Fitness ◽  
Intervention Group ◽  
Interleukin 10 ◽  
Control Group ◽  
Post Intervention ◽  
Necrosis Factor Alpha ◽  
Obese Adolescents ◽  
Quasi Experimental ◽  
Multicomponent Program

Physical exercise reduces the biochemical markers of obesity, but the effects of multicomponent interventions on these markers should be explored. The present study aimed to elucidate how overweight/obese adolescents respond to a multicomponent program approach on body composition, physical fitness, and inflammatory markers, using a quasi-experimental study with 33 overweight/obesity adolescents (control group (CG) = 16; intervention group (IG) = 17). The intervention consisted of 24 weeks with physical exercises and nutritional and psychological guidance. Both groups were evaluated at the pre/post-intervention moments on body mass index (BMI); body fat (%Fat); waist circumference (WC); waist/hip ratio (WHR); waist-to-height ratio (WHtR), cardiorespiratory fitness (CRF); abdominal strength, flexibility; leptin; interleukin 6; interleukin 10; and tumor necrosis factor-alpha. Mixed-analysis of variance and generalized estimation equations were used for statistical analysis. There was an interaction effect between groups and time on %Fat (p = 0.002), WC (p = 0.023), WHR (p < 0.001), WHtR (p = 0.035), CRF (p = 0.050), and leptin (p = 0.026). Adolescents were classified as 82.4% responders for %Fat, 70.6% for WC, 88.2% for WHR, and 70.6% for CRF. Further, there was an association between changes in %Fat (p = 0.033), WC (p = 0.032), and WHR (p = 0.033) between responders and non-responders with CRF in the IG. There was a positive effect on body composition, physical fitness, and leptin. In addition, reductions in body composition parameters were explained by CRF improvements.

scholarly journals Stimulation of Interleukin-10 Production by Acidic β-Lactoglobulin-Derived Peptides Hydrolyzed with Lactobacillus paracasei NCC2461 Peptidases

2004 ◽  
Vol 11 (2) ◽  
pp. 266-271 ◽  
Author(s):  
Guénolée Prioult ◽  
Sophie Pecquet ◽  
Ismail Fliss
Keyword(s):  
Oral Tolerance ◽  
Immunosuppressive Agents ◽  
Interleukin 10 ◽  
Lactobacillus Paracasei ◽  
In Vitro Hydrolysis ◽  
Ifn Γ ◽  
Immunomodulatory Peptides ◽  
Β Lactoglobulin

ABSTRACT We have previously demonstrated that Lactobacillus paracasei NCC2461 may help to prevent cow's milk allergy in mice by inducing oral tolerance to β-lactoglobulin (BLG). To investigate the mechanisms involved in this beneficial effect, we examined the possibility that L. paracasei induces tolerance by hydrolyzing BLG-derived peptides and liberating peptides that stimulate interleukin-10 (IL-10) production. L. paracasei peptidases have been shown to hydrolyze tryptic-chymotryptic peptides from BLG, releasing numerous small peptides with immunomodulating properties. We have now shown that acidic tryptic-chymotryptic peptides stimulate splenocyte proliferation and gamma interferon (IFN-γ) production in vitro. Hydrolysis of these peptides with L. paracasei peptidases repressed the lymphocyte stimulation, up-regulated IL-10 production, and down-regulated IFN-γ and IL-4 secretion. L. paracasei NCC2461 may therefore induce oral tolerance to BLG in vivo by degrading acidic peptides and releasing immunomodulatory peptides stimulating regulatory T cells, which function as major immunosuppressive agents by secreting IL-10.

In vitro effect of ochratoxin A and deoxynivalenol on the expression of interleukin 5 and interferon-gamma in broiler chicken lymphocytes

2016 ◽  
Vol 9 (2) ◽  
pp. 299-304 ◽  
Author(s):  
C. Lautert ◽  
L. Ferreiro ◽  
M.I. Azevedo ◽  
S.A. Botton ◽  
J.T. Santos ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Interferon Gamma ◽  
Broiler Chickens ◽  
Broiler Chicken ◽  
Fungal Metabolites ◽  
Interleukin 5 ◽  
T Helper 2 ◽  
Ifn Γ ◽  
Vitro Effect

Cytokines are proteins secreted by cells of innate and acquired immunity, produced in response to various antigens and responsible for mediating several function of these cells. Our study evaluated the profile of cytokines interleukin 5 (IL-5) and interferon gamma (IFN-γ), induced in lymphocytes of broiler chickens in response to secondary fungal metabolites ochratoxin A (OTA) and deoxynivalenol (DON) at concentrations of 0.001, 0.01, 0.1 and 1 μg/ml. The quantification of the cytokines was analysed at 24, 48 and 72 h after incubation with mycotoxins, using real-time PCR (qRT-PCR). The results obtained showed that OTA induced mRNA synthesis of IL-5 at concentrations 0.001, 0.1 and 1 μg/ml after 24 h of lymphocyte incubation, while at 48 h only the expression of the IL-5 cytokine at a concentration of 1 μg/ml (P<0.05) was detected. DON in a concentration of 1 μg/ml induced the expression of IL-5 in the lymphocytes only at 48 h post-incubation period (P<0.05). Regarding IFN-γ, gene expression was not observed in the lymphocytes of broiler chickens incubated with OTA and DON. The data obtained represent a profile of response mediated by T helper 2 cells to the exposure of broiler chicken immune cells to different concentrations of OTA and DON.

scholarly journals Porcine Choroid Plexus Epithelial Cells Induce Streptococcus suis Bacteriostasis In Vitro

2004 ◽  
Vol 72 (5) ◽  
pp. 3084-3087 ◽  
Author(s):  
Rüdiger A. Adam ◽  
Tobias Tenenbaum ◽  
Peter Valentin-Weigand ◽  
Maurice Laryea ◽  
Bernd Schwahn ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bacterial Meningitis ◽  
Choroid Plexus ◽  
Host Defense ◽  
Streptococcus Suis ◽  
Active Role ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
Choroid Plexus Epithelial

ABSTRACT The involvement of the choroid plexus in host defense during bacterial meningitis is unclear. Aiming to elucidate possible antibacterial mechanisms, we stimulated primary porcine choroid plexus epithelial cells (pCPEC) with proinflammatory cytokines and challenged them with various Streptococcus suis strains. In the supernatant of gamma interferon (IFN-γ)-stimulated pCPEC, streptococcal growth was markedly suppressed. Costimulation with tumor necrosis factor alpha enhanced this bacteriostatic effect, while supplementation of l-tryptophan completely eliminated it. We also demonstrate that an activation of indoleamine 2,3-dioxygenase in the pCPEC seems to be responsible for the IFN-γ-induced bacteriostasis. This supports the hypothesis of an active role of the choroid plexus in host defense against bacterial meningitis.

Interferon resistance of cutaneous T-cell lymphoma–derived clonal T-helper 2 cells allows selective viral replication

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 523-527 ◽  
Author(s):  
Reinhard Dummer ◽  
Udo Döbbeling ◽  
Ralf Geertsen ◽  
Jörg Willers ◽  
Günter Burg ◽  
...  
Keyword(s):  
T Cell ◽  
Viral Replication ◽  
Human Leukocyte ◽  
T Helper ◽  
Cd4 Cells ◽  
Efficient Treatment ◽  
T Helper 2 ◽  
Ifn Γ ◽  
The Impact

Abstract Cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of lymphoproliferative disorders that are characterized by an accumulation of T-lymphocytes in the skin and occasionally in blood known as Sézary syndrome (SS). In most cases the dominant clone displays T-helper 2 cytokines. Because IFN-γ is a natural inhibitor of T-helper 2 cells and IFN-α is frequently used in CTCL, the impact of IFNs on SS-derived purified clonal T-helper 2 cells was studied using anti-Vβ antibodies. Moreover, IFNs are known to mediate virus resistance in normal cells. The isolated clonal CD4+ cells, but not the nonclonal CD4+ cells, appeared resistant to IFN-γ and IFN-α stimulation in terms of human leukocyte antigen up-regulation and MxA induction caused in part by alterations in Stat-1 molecule mRNA and IFNγR1 mRNA transcription. The IFN resistance of the patient-derived clonal cells was then targeted by vesicular stomatitis virus infection after IFN-α priming, resulting in selective viral replication in clonal cells. In contrast, nonclonal cells of the same patient showed IFN-dependent MxA expression, which is a major mediator protein of viral protection. The IFN resistance of the dominant T-helper 2 cells might be important for lymphomagenesis. Interferon signaling deficiencies can be targeted for purging patients' cells in vitro. Furthermore, this approach may allow specific molecular interventions, resulting in the efficient treatment of CTCL and other IFN-resistant neoplasms such as lung cancer.

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