scholarly journals Early Induction of Gamma Interferon and Interleukin-10 Production in Draining Lymph Nodes from Mice Infected withBorrelia burgdorferi

2000 ◽  
Vol 68 (12) ◽  
pp. 7162-7165 ◽  
Author(s):  
Frederic Ganapamo ◽  
Vida A. Dennis ◽  
Mario T. Philipp
Keyword(s):  
Differential Susceptibility ◽  
Neutralizing Antibody ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Lyme Arthritis ◽  
Ifn Γ ◽  
Culture Supernatants ◽  
Draining Lymph Nodes ◽  
Cells Cultured

ABSTRACT Lymph node (LN) cells from C3H/HeJ mice (Lyme disease susceptible) infected for 1 week with Borrelia burgdorferi strain JD1 produced higher levels of gamma interferon (IFN-γ) when stimulated in vitro with B. burgdorferi spirochetes than equivalent cells from B. burgdorferi-infected C57BL/6J mice (disease resistant). The interleukin-10 (IL-10) levels were comparable in the two strains, whereas the IL-4 levels were below detection limits.B. burgdorferi-stimulated LN cells from C57BL/6J mice produced significantly higher levels of IFN-γ in the presence of neutralizing anti-IL-10 antibody than cells cultured with B. burgdorferi alone. No effect of IL-10 neutralization on IFN-γ production by LN cells from C3H/HeJ mice was observed. Neutralizing antibody to IFN-γ had no effect on the production of IL-10 by LN cells from C57BL/6J mice. A slight decrease in IL-10 production was detected in culture supernatants of equivalent cells from C3H/HeJ mice. The differential effect of IL-10 on IFN-γ production in C57BL/6J and C3H/HeJ mice suggests that IL-10 is probably involved in the regulation of IFN-γ production by LN cells during infection and may be at the root of the differential susceptibility to Lyme arthritis in these two strains of mice.

scholarly journals Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival of Mycobacterium avium subsp. paratuberculosis in Monocyte-Derived Macrophages from Naturally Infected Cattle

2004 ◽  
Vol 72 (4) ◽  
pp. 1974-1982 ◽  
Author(s):  
M. S. Khalifeh ◽  
J. R. Stabel
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Mycobacterium Avium ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Culture Supernatants

ABSTRACT Gamma interferon (IFN-γ) plays a significant role in the control of mycobacterial infections, including Mycobacterium avium subsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. avium subsp. paratuberculosis on the production of IFN-γ, IL-10, and TGF-β by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-γ, IL-10, and TGF-β on M. avium subsp. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-β in culture supernatants in response to stimulation with live M. avium subsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-β, but after stimulation with live M. avium subsp. paratuberculosis, TGF-β levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. avium subsp. paratuberculosis recovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. avium subsp. paratuberculosis. The addition of exogenous IL-10 and TGF-β to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. avium subsp. paratuberculosis recovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-β during infection with M. avium subsp. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. avium subsp. paratuberculosis.

scholarly journals Legionella pneumophila Evades Gamma Interferon-Mediated Growth Suppression through Interleukin-10 Induction in Bone Marrow-Derived Macrophages

2005 ◽  
Vol 73 (5) ◽  
pp. 2709-2717 ◽  
Author(s):  
Sadako Yoshizawa ◽  
Kazuhiro Tateda ◽  
Tetsuya Matsumoto ◽  
Fumio Gondaira ◽  
Shuichi Miyazaki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cross Talk ◽  
Legionella Pneumophila ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Protein Component ◽  
Interleukin 12 ◽  
Cellular Mechanisms ◽  
Ifn Γ ◽  
Culture Supernatants

ABSTRACT We examined the roles of Th1-Th2 cytokine cross talk in Legionella pneumophila-infected bone marrow-derived (BM) macrophages in the presence of costimulation with interleukin-12 (IL-12) and IL-18. Treatment with gamma interferon (IFN-γ) alone or treatment with IL-12 in combination with IL-18 resulted in a 3- or 2-log reduction in bacterial numbers, respectively, in BM macrophages, whereas treatment with IL-12 or IL-18 alone had no effect. Significant amounts of IFN-γ were detected in the culture supernatants of infected macrophages stimulated with IL-12 and IL-18 in combination but not independently. Neutralization of IFN-γ by antibody completely abolished the growth inhibitory effects of IL-12 and IL-18. Interestingly, higher infectivity ratios of L. pneumophila or the addition of increasing concentrations of heat-killed bacteria (HKB) suppressed the production of IFN-γ, which resulted in the increased intracellular growth of bacteria. Significant amounts of IL-10 were detected in culture supernatants when Legionella-infected macrophages were cocultured with HKB. Furthermore, neutralization of IL-10 by antibody resulted in an increase in IFN-γ production by infected BM macrophages when cocultured with HKB. Treatment of HKB with trypsin but not polymyxin B attenuated the growth-promoting effects of HKB, suggesting the involvement of a protein component(s) in regulation of the growth of L. pneumophila. These findings demonstrate a crucial role of Th1-Th2 cross talk in L. pneumophila-infected BM macrophages. Our results also suggest that L. pneumophila modulates the cytokine balance from IFN-γ-driven Th1 to more Th2 responses, likely through the induction of IL-10 by a bacterial protein component(s). These data provide new insights not only into the cellular mechanisms of Th1-Th2 cross talk in Legionella-infected macrophages but also into the pathogenesis of L. pneumophila pneumonia in humans.

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 Neutralization of Interleukin-10 Significantly Enhances Gamma Interferon Expression in Peripheral Blood by Stimulation with Johnin Purified Protein Derivative and by Infection with Mycobacterium avium subsp. paratuberculosis in Experimentally Infected Cattle with Paratuberculosis

2004 ◽  
Vol 72 (4) ◽  
pp. 2425-2428 ◽  
Author(s):  
Joram J. Buza ◽  
Hirokazu Hikono ◽  
Yasuyuki Mori ◽  
Reiko Nagata ◽  
Sachiyo Hirayama ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Suppressive Effect ◽  
Gamma Interferon ◽  
Peripheral Blood Mononuclear ◽  
Purified Protein Derivative ◽  
Ifn Γ

ABSTRACT Monoclonal antibody neutralization of interleukin-10 (IL-10) increased Johnin purified protein derivative-induced whole-blood gamma interferon (IFN-γ) secretion 23-fold and also increased IFN-γ secretion ninefold following in vitro Mycobacterium avium subsp. paratuberculosis infection of peripheral blood mononuclear cells. These results demonstrate the suppressive effect of IL-10 on immune responses to M. avium subsp. paratuberculosis infection in cattle.

scholarly journals Monocyte-Derived Interleukin-10 Depresses the Bordetella pertussis- Specific Gamma Interferon Response in Vaccinated Infants

2009 ◽  
Vol 16 (12) ◽  
pp. 1816-1821 ◽  
Author(s):  
V. Dirix ◽  
V. Verscheure ◽  
T. Goetghebuer ◽  
M. Hainaut ◽  
A. S. Debrie ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Bordetella Pertussis ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Interferon Response ◽  
Ifn Γ

ABSTRACT Antigen-specific gamma interferon (IFN-γ) has been demonstrated to participate in protection against Bordetella pertussis infection. Circulating mononuclear cells from B. pertussis-infected and from pertussis-vaccinated infants secrete high amounts of IFN-γ after in vitro stimulation by B. pertussis antigens, but with a large variation in the secreted IFN-γ levels between individuals. We show here that the inhibition of the specific IFN-γ response can be at least partially attributed to IL-10 secretion by monocytes. This IL-10 secretion was not associated with polymorphisms at positions −1082, −819, and −592 of the IL-10 gene promoter, suggesting that other genetic or environmental factors affect IL-10 expression and secretion.

scholarly journals Enhanced Murine Antigen-Specific Gamma Interferon and Immunoglobulin G2a Responses by Using Mycobacterial ESAT-6 Sequences in DNA Vaccines

2003 ◽  
Vol 71 (4) ◽  
pp. 2239-2243 ◽  
Author(s):  
F. Chris Minion ◽  
Sreekumar A. Menon ◽  
Gregory G. Mahairas ◽  
M. J. Wannemuehler
Keyword(s):  
Immune Responses ◽  
Dna Vaccines ◽  
Serum Antibody ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Viral Pathogens ◽  
Ifn Γ ◽  
Antibody Levels

ABSTRACT The Mycobacterium tuberculosis protein ESAT-6 has unusual immune stimulating activities, has been implicated in the recall of long-lived immunity, and induces protection against tuberculosis in mice. For many diseases caused by bacterial or viral pathogens, a strong cell-mediated immune (i.e., type 1) response is often required for recovery or protection. Therefore, it is important to design immunization regimens that induce agent-specific type 1 immunity. We have shown in previous studies that ESAT-6 could enhance antigen-specific type 1 immune responses in BALB/c mice against a second antigen when presented as a purified fusion protein. It was also of interest to determine if ESAT-6 could enhance the type 1 response against a second antigen beyond that afforded by DNA vaccination through CpG motifs. This was tested by using gene fusions of ESAT-6 and the Mycoplasma hyopneumoniae surface antigen P71. Modified P71 gene sequences were cloned with or without ESAT-6 sequences into a DNA vaccine vector and were used to immunize mice. Splenic lymphocytes from vaccinated mice were tested for gamma interferon (IFN-γ) and interleukin-10 (IL-10) secretion. Serum antibodies were examined for P71 antigen-specific isotype responses. When stimulated in vitro with purified P71 antigen, splenocytes from the ESAT-6:P71 vaccinates secreted higher levels of IFN-γ and lower levels of IL-10 compared to those of vaccinates receiving the P71 construct alone. Furthermore, the immunoglobulin G2a serum antibody levels were significantly higher in the ESAT-6:P71 vaccinates compared to those of the vaccinates receiving P71 alone. In conclusion, ESAT-6 was shown to enhance antigen-specific type 1 immune responses in BALB/c mice when used in DNA vaccines.

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.

scholarly journals Regulatory T Cells Contribute to Resistance against Lyme Arthritis

2020 ◽  
Vol 88 (11) ◽  
Author(s):  
Emily M. Siebers ◽  
Elizabeth S. Liedhegner ◽  
Michael W. Lawlor ◽  
Ronald F. Schell ◽  
Dean T. Nardelli
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lyme Disease ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Interleukin 10 ◽  
Lyme Arthritis ◽  
Interleukin 17 ◽  
Content Type

ABSTRACT The symptoms of Lyme disease are caused by inflammation induced by species of the Borrelia burgdorferi sensu lato complex. The various presentations of Lyme disease in the population suggest that differences exist in the intensity and regulation of the host response to the spirochete. Previous work has described correlations between the presence of regulatory T cells and recovery from Lyme arthritis. However, the effects of Foxp3-expressing CD4+ T cells existing prior to, and during, B. burgdorferi infection have not been well characterized. Here, we used C57BL/6 “depletion of regulatory T cell” mice to assess the effects these cells have on the arthritis-resistant phenotype characteristic of this mouse strain. We showed that depletion of regulatory T cells prior to infection with B. burgdorferi resulted in sustained swelling, as well as histopathological changes, of the tibiotarsal joints that were not observed in infected control mice. Additionally, in vitro stimulation of splenocytes from these regulatory T cell-depleted mice resulted in increases in gamma interferon and interleukin-17 production and decreases in interleukin-10 production that were not evident among splenocytes of infected mice in which Treg cells were not depleted. Depletion of regulatory T cells at various times after infection also induced rapid joint swelling. Collectively, these findings provide evidence that regulatory T cells existing at the time of, and possibly after, B. burgdorferi infection may play an important role in limiting the development of arthritis.

scholarly journals Toll-Like Receptor 2 Controls the Gamma Interferon Response to Francisella tularensis by Mouse Liver Lymphocytes

2007 ◽  
Vol 75 (11) ◽  
pp. 5338-5345 ◽  
Author(s):  
Kee-Jong Hong ◽  
Jason R. Wickstrum ◽  
Hung-Wen Yeh ◽  
Michael J. Parmely
Keyword(s):  
Francisella Tularensis ◽  
Cell Types ◽  
Gamma Interferon ◽  
Interferon Response ◽  
Interleukin 12 ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT The production of gamma interferon (IFN-γ) is a key step in the protective innate immune response to Francisella tularensis. Natural killer cells and T cells in the liver are important sources of this cytokine during primary F. tularensis infections, and interleukin-12 (IL-12) appears to be an essential coactivating cytokine for hepatic IFN-γ expression. The present study was undertaken to determine whether or not macrophages (Mφ) or dendritic cells (DC) provide coactivating signals for the liver IFN-γ response in vitro, whether IL-12 mediates these effects, and whether Toll-like receptor (TLR) signaling is essential to induce this costimulatory activity. Both bone marrow-derived Mφ and DC significantly augmented the IFN-γ response of F. tularensis-challenged liver lymphocytes in vitro. While both cell types produced IL-12p40 in response to F. tularensis challenge, only DC secreted large quantities of IL-12p70. DC from both IL-12p35-deficient and TLR2-deficient mice failed to produce IL-12p70 and did not costimulate liver lymphocytes for IFN-γ production in response to viable F. tularensis organisms. Conversely, liver lymphocytes from TLR2-deficient mice cocultured with wild-type accessory cells produced IFN-γ at levels comparable to those for wild-type hepatic lymphocytes. These findings indicate that TLR2 controls hepatic lymphocyte IFN-γ responses to F. tularensis by regulating DC IL-12 production. While Mφ also coinduced hepatic IFN-γ production in response to F. tularensis, they did so in a fashion less dependent on TLR2.

scholarly journals Gamma Interferon Mediates Experimental Cerebral Malaria by Signaling within Both the Hematopoietic and Nonhematopoietic Compartments

2017 ◽  
Vol 85 (11) ◽  
Author(s):  
Ana Villegas-Mendez ◽  
Patrick Strangward ◽  
Tovah N. Shaw ◽  
Ivana Rajkovic ◽  
Vinko Tosevski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cerebral Malaria ◽  
Myeloid Cell ◽  
Gamma Interferon ◽  
Cell Populations ◽  
Experimental Cerebral Malaria ◽  
Cerebral Pathology ◽  
Multiple Cell ◽  
Ifn Γ

ABSTRACT Experimental cerebral malaria (ECM) is a gamma interferon (IFN-γ)-dependent syndrome. However, whether IFN-γ promotes ECM through direct and synergistic targeting of multiple cell populations or by acting primarily on a specific responsive cell type is currently unknown. Here, using a panel of cell- and compartment-specific IFN-γ receptor 2 (IFN-γR2)-deficient mice, we show that IFN-γ causes ECM by signaling within both the hematopoietic and nonhematopoietic compartments. Mechanistically, hematopoietic and nonhematopoietic compartment-specific IFN-γR signaling exerts additive effects in orchestrating intracerebral inflammation, leading to the development of ECM. Surprisingly, mice with specific deletion of IFN-γR2 expression on myeloid cells, T cells, or neurons were completely susceptible to terminal ECM. Utilizing a reductionist in vitro system, we show that synergistic IFN-γ and tumor necrosis factor (TNF) stimulation promotes strong activation of brain blood vessel endothelial cells. Combined, our data show that within the hematopoietic compartment, IFN-γ causes ECM by acting redundantly or by targeting non-T cell or non-myeloid cell populations. Within the nonhematopoietic compartment, brain endothelial cells, but not neurons, may be the major target of IFN-γ leading to ECM development. Collectively, our data provide information on how IFN-γ mediates the development of cerebral pathology during malaria infection.

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