scholarly journals Modulation of Gamma Interferon Receptor 1 by Mycobacterium tuberculosis: a Potential Immune Response Evasive Mechanism

2007 ◽  
Vol 75 (5) ◽  
pp. 2500-2510 ◽  
Author(s):  
Amit Singhal ◽  
Anand Jaiswal ◽  
Virendra K. Arora ◽  
Hanumanthappa K. Prasad
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Surface Expression ◽  
Gamma Interferon ◽  
Mobility Shift ◽  
Down Regulation ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Mycobacterium tuberculosis inhibits gamma interferon (IFN-γ)-mediated antimycobacterial action by adopting diverse mechanisms. IFN-γ binds to its receptor, IFN-γR, in order to initiate proper signaling. We have observed reduced surface expression levels of IFN-γ receptor 1 (IFN-γR1) in untreated pulmonary tuberculosis patients compared to those in healthy individuals (P < 0.01). Following antitubercular therapy, the expression of IFN-γR1 was restored in these patients. To delineate the mechanism by which M. tuberculosis modulates IFN-γR1, in vitro experiments were designed, wherein the down modulation of IFN-γR1 surface expression was observed for CD14+ cells in peripheral blood mononuclear cells (PBMCs) cocultured with live M. tuberculosis compared to that for uninfected cells (P < 0.01). No modulation of IFN-γR1 expression was observed for CD14+ cells in PBMCs infected with Mycobacterium smegmatis. A time-dependent decrease in IFN-γR1 mRNA expression was observed for PBMCs infected with M. tuberculosis. Similar down modulation of IFN-γR1 protein and mRNA expression in phorbol myristate acetate-differentiated THP-1 cells (pdTHP-1) by M. tuberculosis was observed (P < 0.01). Using reporter gene analysis of 5′ deletion constructs of the IFN-γR1 gene (IFNGR1) promoter, the decrease in IFN-γR1 mRNA in M. tuberculosis-infected pdTHP-1 cells was shown to be due to the decreased transcription of IFNGR1. By immunoblotting and electrophoretic mobility shift assays, the down regulation of stimulating protein 1 (Sp1) expression and its recruitment on the phorbol ester-responsive element of the IFNGR1 promoter in M. tuberculosis-infected pdTHP-1 cells was observed. This down regulation of Sp1 in pdTHP-1 cells cocultured with M. tuberculosis may be responsible for the down regulation of IFN-γR1 expression, thereby potentially altering its receptivity to IFN-γ.

scholarly journals Failure of Gamma Interferon but Not Interleukin-10 Expression in Response to Human Papillomavirus Type 11 E6 Protein in Respiratory Papillomatosis

2004 ◽  
Vol 11 (3) ◽  
pp. 538-547 ◽  
Author(s):  
James A. DeVoti ◽  
Bettie M. Steinberg ◽  
David W. Rosenthal ◽  
Lynda Hatam ◽  
Andrea Vambutas ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 2 ◽  
Cytokine Expression ◽  
Gamma Interferon ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Recurrent respiratory papillomatosis (RRP) is a chronic, debilitating disease of the upper airway caused by human papillomavirus type 6 (HPV-6) or HPV-11. We describe responses of peripheral blood mononuclear cells (PBMC) and T cells from RRP patients and controls to the HPV-11 early proteins E6 and E7. PBMC were exposed in vitro to purified E6 or E7 proteins or transduced with fusion proteins containing the first 11 amino acids of the human immunodeficiency virus type 1 protein tat fused to E6 or E7 (tat-E6/tat-E7). TH1-like (interleukin-2 [IL-2], gamma interferon [IFN-γ], IL-12, and IL-18), and TH2-like (IL-4 and IL-10) cytokine mRNAs were identified by reverse transcription-PCR, and IFN-γ and IL-10 cytokine-producing cells were identified by enzyme-linked immunospot assay. These studies show that HPV-11 E6 skews IL-10-IFN-γ expression by patients with RRP toward greater expression of IL-10 than of IFN-γ. In addition, there is a general cytokine hyporesponsiveness to E6 that is more prominent for TH1-like cytokine expression by patients with severe disease. Patients showed persistent IL-10 cytokine expression by the nonadherent fraction of PBMC when challenged with E6 and tat-E6, and, in contrast to controls, both T cells and non-T cells from patients expressed IL-10. However, E7/tat-E7 cytokine responses in patients with RRP were similar to those of the controls. In contrast, E6 inhibited IL-2 and IL-18 mRNA expression that would further contribute to a cytokine microenvironment unfavorable to HPV-specific, T-cell responses that should control persistent HPV infection. In summary, E6 is the dominant inducer of cytokine expression in RRP, and it induces a skewed expression of IL-10 compared to the expression of IFN-γ.

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 Regulation of Interferon-γ receptor (IFN-γR) expression in macrophages during Mycobacterium tuberculosis infection

2020 ◽  
Vol 11 (1) ◽  
pp. 76-85
Author(s):  
Gunjan Kak ◽  
Brijendra K Tiwari ◽  
Yogendra Singh ◽  
Krishnamurthy Natarajan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mononuclear Cells ◽  
Second Messengers ◽  
Surface Expression ◽  
Interferon Γ ◽  
Fine Tuning ◽  
Mycobacterium Tuberculosis Infection ◽  
Peripheral Blood Mononuclear ◽  
Negative Role ◽  
Ifn Γ

AbstractInterferon-gamma (IFN-γ) is a key cytokine that mediates immunity to tuberculosis (TB). Mycobacterium tuberculosis (M. tb) is known to downregulate the surface expression of IFN-γ receptor (IFN-γR) on macrophages and peripheral blood mononuclear cells (PBMCs) of patients with active TB disease. Many M. tb antigens also downmodulate IFN-γR levels in macrophages when compared with healthy controls. In the current study, we aimed at deciphering key factors involved in M. tb mediated downregulation of IFN-γR levels on macrophage surface. Our data showed that both M. tb H37Rv and M. bovis BCG infections mediate downmodulation of IFN-γR on human macrophages. This downmodulation is regulated at the level of TLR signaling pathway, second messengers such as calcium and cellular kinases i.e. PKC and ERK-MAPK, indicating that fine tuning of calcium response is critical to maintaining IFN-γR levels on macrophage surface. In addition, genes in the calcium and cysteine protease pathways which were previously identified by us to play a negative role during M. tb infection, also regulated IFN-γR expression. Thus, modulations in IFN-γR levels by utilizing host machinery may be a key immune suppressive strategy adopted by the TB pathogen to ensure its persistence and thwart host defense.

scholarly journals Contribution of Each of Four Superantigens to Streptococcus equi-Induced Mitogenicity, Gamma Interferon Synthesis, and Immunity

2010 ◽  
Vol 78 (4) ◽  
pp. 1728-1739 ◽  
Author(s):  
Romain Paillot ◽  
Carl Robinson ◽  
Karen Steward ◽  
Nicola Wright ◽  
Thibaud Jourdan ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Gamma Interferon ◽  
Mitogenic Activity ◽  
Peripheral Blood Mononuclear ◽  
Allelic Replacement ◽  
Neutralizing Capacity ◽  
Streptococcus Equi ◽  
Ifn Γ ◽  
Dose Dependent

ABSTRACT Streptococcus equi is the causative agent of strangles, the most frequently diagnosed infectious disease of horses worldwide. The disease is characterized by abscessation and swelling of the lymph nodes of the head and neck, which can literally strangle the horse to death. S. equi produces four recently acquired phage-associated bacterial superantigens (sAgs; SeeH, SeeI, SeeL, and SeeM) that share homology with the mitogenic toxins of Streptococcus pyogenes. The aim of this study was to characterize the contribution of each of these S. equi sAgs to mitogenic activity in vitro and quantify the sAg-neutralizing capacity of sera from naturally infected horses in order to better understand their role in pathogenicity. Each of the sAgs was successfully cloned, and soluble proteins were produced in Escherichia coli. SeeI, SeeL, and SeeM induced a dose-dependent proliferative response in equine CD4 T lymphocytes and synthesis of gamma interferon (IFN-γ). SeeH did not stimulate equine peripheral blood mononuclear cells (PBMC) but induced proliferation of asinine PBMC. Allelic replacement mutants of S. equi strain 4047 with sequential deletion of the superantigen genes were generated. Deletion of seeI, seeL, and seeM completely abrogated the mitogenic activity and synthesis of IFN-γ, in equine PBMC, of the strain 4047 culture supernatant. Sera from naturally infected convalescent horses had only limited sAg-neutralizing activities. We propose that S. equi sAgs play an important role in S. equi pathogenicity by stimulating an overzealous and inappropriate Th1 response that may interfere with the development of an effective immune response.

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 Cellular Immune Responses to ESAT-6 Discriminate between Patients with Pulmonary Disease Due to Mycobacterium avium Complex and Those with Pulmonary Disease Due toMycobacterium tuberculosis

1999 ◽  
Vol 6 (4) ◽  
pp. 606-609 ◽  
Author(s):  
A. David Lein ◽  
C. Fordham von Reyn ◽  
Pernille Ravn ◽  
C. Robert Horsburgh ◽  
Lorraine N. Alexander ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Disease ◽  
Mycobacterium Avium ◽  
Mononuclear Cells ◽  
Negative Control ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of theMycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-γ) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary disease due to eitherMycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-γ responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0 (0%) of 8 controls. Significant IFN-γ responses to M. tuberculosis purified protein derivative were detected in 23 (85%) of 27 M. tuberculosisdisease patients, 2 (25%) of 8 MAC disease patients, and 5 (63%) of 8 healthy controls. M. avium sensitin was recognized in 24 (89%) of 27 M. tuberculosis disease patients, 4 (50%) of 8 MAC disease patients, and 1 (13%) of 8 controls. IFN-γ responses to ESAT-6 are specific for disease due toM. tuberculosis and are not observed in patients with MAC disease or in healthy controls.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Inflammatory Infiltration ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Inflammatory Damage ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

scholarly journals Protection of BALB/c Mice against Brucella abortus 544 Challenge by Vaccination with Bacterioferritin or P39 Recombinant Proteins with CpG Oligodeoxynucleotides as Adjuvant

2001 ◽  
Vol 69 (8) ◽  
pp. 4816-4822 ◽  
Author(s):  
Ayman Al-Mariri ◽  
Anne Tibor ◽  
Pascal Mertens ◽  
Xavier De Bolle ◽  
Patrick Michel ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Brucella Abortus ◽  
Mononuclear Cells ◽  
Brucella Melitensis ◽  
Cpg Odn ◽  
Peripheral Blood Mononuclear ◽  
Recombinant Antigens ◽  
Cpg Oligodeoxynucleotides ◽  
Ifn Γ

ABSTRACT The P39 and the bacterioferrin (BFR) antigens of Brucella melitensis 16M were previously identified as T dominant antigens able to induce both delayed-type hypersensivity in sensitized guinea pigs and in vitro gamma interferon (IFN-γ) production by peripheral blood mononuclear cells from infected cattle. Here, we analyzed the potential for these antigens to function as a subunitary vaccine against Brucella abortus infection in BALB/c mice, and we characterized the humoral and cellular immune responses induced. Mice were injected with each of the recombinant proteins alone or adjuvanted with either CpG oligodeoxynucleotides (CpG ODN) or non-CpG ODN. Mice immunized with the recombinant antigens with CpG ODN were the only group demonstrating both significant IFN-γ production and T-cell proliferation in response to either Brucella extract or to the respective antigen. The same conclusion holds true for the antibody response, which was only demonstrated in mice immunized with recombinant antigens mixed with CpG ODN. The antibody titers (both immunoglobulin G1 [IgG1] and IgG2a) induced by P39 immunization were higher than the titers induced by BFR (only IgG2a). Using a B. abortus 544 challenge, the level of protection was analyzed and compared to the protection conferred by one immunization with the vaccine strain B19. Immunization with P39 and CpG ODN gave a level of protection comparable to the one conferred by B19 at 4 weeks postchallenge, and the mice were still significantly protected at 8 weeks postchallenge, although to a lesser extent than the B19-vaccinated group. Intriguingly, no protection was detected after BFR vaccination. All other groups did not demonstrate any protection.

scholarly journals Evaluation of Immunostimulatory Activities of Synthetic Mannose-Containing Structures Mimicking the β-(1→2)-Linked Cell Wall Mannans of Candida albicans

2012 ◽  
Vol 19 (11) ◽  
pp. 1889-1893 ◽  
Author(s):  
Kaarina Ranta ◽  
Kaisa Nieminen ◽  
Filip S. Ekholm ◽  
Moniká Poláková ◽  
Mattias U. Roslund ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Mouse Macrophages ◽  
Ifn Γ ◽  
Low Levels ◽  
Necrosis Factor

ABSTRACTImmunostimulatory properties of synthetic structures mimicking the β-(1→2)-linked mannans ofCandida albicanswere evaluatedin vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-d-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).

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