13 results on '"Jacobs, Muazzam"'
Search Results
2. Tumor necrosis factor is critical to control tuberculosis infection.
- Author
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Jacobs M, Togbe D, Fremond C, Samarina A, Allie N, Botha T, Carlos D, Parida SK, Grivennikov S, Nedospasov S, Monteiro A, Le Bert M, Quesniaux V, and Ryffel B
- Subjects
- Animals, Humans, Mycobacterium tuberculosis immunology, Tuberculosis physiopathology, Tumor Necrosis Factors deficiency, Tumor Necrosis Factors immunology, Mycobacterium tuberculosis physiology, Tuberculosis immunology, Tumor Necrosis Factors physiology
- Abstract
Tumor necrosis factor (TNF) is critical and non-redundant to control Mycobacterium tuberculosis infection and cannot be replaced by other proinflammatory cytokines. Overproduction of TNF may cause immunopathology, while TNF neutralization reactivates latent and chronic, controlled infection, which is relevant for the use of neutralizing TNF therapies in patients with rheumatoid arthritis.
- Published
- 2007
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3. T cell-derived TNF down-regulates acute airway response to endotoxin.
- Author
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Togbe D, Grivennikov SI, Noulin N, Couillin I, Maillet I, Jacobs M, Maret M, Fick L, Nedospasov SA, Quesniaux VF, Schnyder B, and Schnyder-Candrian S
- Subjects
- Administration, Inhalation, Animals, Bronchi pathology, Cells, Cultured, Endotoxins antagonists & inhibitors, Lung pathology, Mice, Mice, Inbred C57BL, Plethysmography, Whole Body, T-Lymphocytes immunology, Bronchi immunology, Down-Regulation immunology, Endotoxins toxicity, Lung immunology, T-Lymphocytes metabolism, Tumor Necrosis Factors physiology
- Abstract
Acute and chronic airway inflammations caused by environmental agents including endotoxin represent an increasing health problem. Local TNF production may contribute to lung dysfunction and inflammation, although pulmonary neutrophil recruitment occurs in the absence of TNF. First, we demonstrate that membrane-bound TNF is sufficient to mediate the inflammatory responses to lipopolysaccharide (LPS). Secondly, using cell type-specific TNF-deficient mice we show that TNF derived from either macrophage/neutrophil (M/N) or T lymphocytes have differential effects on LPS-induced respiratory dysfunction (enhanced respiratory pause, Penh) and pulmonary neutrophil recruitment. While Penh, vascular leak, neutrophil recruitment, TNF, and thymus- and activation-regulated chemokine/CCL17 (TARC) expression in the lung were reduced in M/N-deficient mice, T cell-specific TNF-deficient mice displayed augmented Penh, vascular leak, neutrophil influx, increased CD11c+ cells and expression of TNF, TARC and murine CXC chemokines KC/CXCL1 in the lung. In conclusion, inactivation of TNF in either M/N or T cells has differential effects on LPS-induced lung disease, suggesting that selective deletion of TNF in T cells may aggravate airway pathology.
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- 2007
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4. Tumor Necrosis Factor (TNF) Receptor-1 (TNFp55) Signal Transduction and Macrophage-Derived Soluble TNF Are Crucial for Nitric Oxide-Mediated Trypanosoma congolense Parasite Killing
- Author
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Magez, Stefan, Radwanska, Magdalena, Drennan, Michael, Fick, Lizette, Baral, Toya Nath, Allie, Nasiema, Jacobs, Muazzam, Nedospasov, Sergei, Brombacher, Frank, Ryffel, Bernard, and De Baetselier, Patrick
- Published
- 2007
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5. Complete ablation of tumor necrosis factor decreases the production of IgA, IgG, and IgM in experimental central nervous system tuberculosis.
- Author
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Francisco, Ngiambudulu M., Allie, Nasiema, Sebesho, Boipelo, Ryffel, Bernhard, and Jacobs, Muazzam
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TUMOR necrosis factors ,CENTRAL nervous system ,FACTORS of production ,TUBERCULOSIS ,B cells - Abstract
Objective(s): This study aimed to explore the contribution of tumor necrosis factor (TNF) in the recruitment of B-cell and secretion of immunoglobulins (Igs) during cerebral tuberculosis (TB). Materials and Methods: In this work, the contributing role of TNF in regulating Ig secretions was investigated by comparing wild type TNF (TNF
f/f ), B-cell-derived TNF (BTNF-/- ), and complete TNF ablation (TNF-/- ) in a mouse cerebral Mycobacterium tuberculosis infection. Using flow cytometry and ELISA, we were able to examine the recruitment of B-cell subsets, and the production of Igs; also assessed the expression of surface markers on B cell subsets. Results: Here, we found that TNF-/- mice showed defective expression of IgA, IgG, and IgM antibodies compared with TNFf/f and BTNF-/- mice, which was significantly decreased in the expression of surface markers and co-stimulatory molecules. Moreover, mice that produced low antibody levels were not able to control infection, therefore progressed to disease; providing direct evidence for the TNF gene-regulating humoral immunity during central nervous system (CNS) M. tuberculosis infection. In contrast, BTNF-/- mice controlled the infection and had levels of IgA, IgG, and IgM comparable to TNFf/f mice. Conclusion: Together, our results demonstrate that TNF may serve as an essential regulator of antibody-mediated immune responses in CNS TB. However, the protective level exhibited by TNFproducing B cells could be defined as baseline protection that could be used in the development of new therapeutic targets or designing new vaccines. [ABSTRACT FROM AUTHOR]- Published
- 2020
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6. Roles of soluble and membrane TNF and related ligands in mycobacterial infections: effects of selective and non-selective TNF inhibitors during infection
- Author
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Garcia, Irene, Olleros, Maria L, Quesniaux, Valérie, Jacobs, Muazzam, Allie, Nasiema, Nedospasov, Sergei A, Szymkowski, David E, Ryffel, Bernhard, Department of Pathology and Immunology, Univ. Geneva, University of Geneva [Switzerland], Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, and Xencor
- Subjects
Mycobacterium Infections ,MESH: Humans ,Cell Membrane ,MESH: Tumor Necrosis Factors ,Ligands ,MESH: Lymphotoxin-alpha ,MESH: Solubility ,Solubility ,Tumor Necrosis Factors ,MESH: Ligands ,Animals ,Humans ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Tumor Necrosis Factor Inhibitors ,MESH: Animals ,MESH: Mycobacterium Infections ,Lymphotoxin-alpha ,ComputingMilieux_MISCELLANEOUS ,MESH: Cell Membrane - Abstract
International audience
- Published
- 2011
7. Myeloid and T Cell-Derived TNF Protects against Central Nervous System Tuberculosis.
- Author
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Nai-Jen Hsu, Francisco, Ngiambudulu M., Keeton, Roanne, Allie, Nasiema, Quesniaux, Valérie F. J., Ryffel, Bernhard, and Jacobs, Muazzam
- Subjects
CENTRAL nervous system diseases ,TUBERCULOSIS complications ,TUMOR necrosis factors ,GENETICS - Abstract
Tuberculosis of the central nervous system (CNS-TB) is a devastating complication of tuberculosis, and tumor necrosis factor (TNF) is crucial for innate immunity and controlling the infection. TNF is produced by many cell types upon activation, in particularly the myeloid and T cells during neuroinflammation. Here we used mice with TNF ablation targeted to myeloid and T cell (MT-TNF
-/- ) to assess the contribution of myeloid and T cell-derived TNF in immune responses during CNS-TB. These mice exhibited impaired innate immunity and high susceptibility to cerebral Mycobacterium tuberculosis infection, a similar phenotype to complete TNF-deficient mice. Further, MT-TNF-/- mice were not able to control T cell responses and cytokine/chemokine production. Thus, our data suggested that collective TNF production by both myeloid and T cells are required to provide overall protective immunity against CNS-TB infection. [ABSTRACT FROM AUTHOR]- Published
- 2017
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8. TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis.
- Author
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Francisco, Ngiambudulu M., Nai-Jen Hsu, Keeton, Roanne, Randall, Philippa, Sebesho, Boipelo, Allie, Nasiema, Govender, Dhirendra, Quesniaux, Valerie, Ryffel, Bernhard, Kellaway, Lauriston, and Jacobs, Muazzam
- Subjects
NATURAL immunity ,CENTRAL nervous system diseases ,MYCOBACTERIUM tuberculosis ,TUMOR necrosis factors ,NEURAL physiology ,PHYSIOLOGY - Abstract
Background: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. Methods: We generated neuron-specific TNF-deficient (NsTNF
) mice and compared outcomes of disease against TNF-/- f/f control and global TNF-/- mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). Results: Intracerebral M. tuberculosis infection of TNF-/- mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF-/- mice were resistant to infection and presented with a phenotype similar to that in TNFf/f control mice. Impaired immunity in TNF-/- mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. Conclusion: Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB. [ABSTRACT FROM AUTHOR]- Published
- 2015
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9. Reactivation of M. tuberculosis Infection in Trans-Membrane Tumour Necrosis Factor Mice.
- Author
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Dambuza, Ivy, Keeton, Roanne, Allie, Nasiema, Hsu, Nai-Jen, Randall, Philippa, Sebesho, Boipelo, Fick, Lizette, Quesniaux, Valerie J. F., and Jacobs, Muazzam
- Subjects
TUBERCULOSIS ,TUMORS ,TUMOR necrosis factors ,DRUG therapy ,MEDICAL research - Abstract
Of those individuals who are infected with M. tuberculosis, 90% do not develop active disease and represents a large reservoir of M. tuberculosis with the potential for reactivation of infection. Sustained TNF expression is required for containment of persistent infection and TNF neutralization leads to tuberculosis reactivation. In this study, we investigated the contribution of soluble TNF (solTNF) and transmembrane TNF (Tm-TNF) in immune responses generated against reactivating tuberculosis. In a chemotherapy induced tuberculosis reactivation model, mice were challenged by aerosol inhalation infection with low dose M. tuberculosis for three weeks to establish infection followed chemotherapeutic treatment for six weeks, after which therapy was terminated and tuberculosis reactivation investigated. We demonstrate that complete absence of TNF results in host susceptibility to M. tuberculosis reactivation in the presence of established mycobacteria-specific adaptive immunity with mice displaying unrestricted bacilli growth and diffused granuloma structures compared to WT control mice. Interestingly, bacterial re-emergence is contained in Tm-TNF mice during the initial phases of tuberculosis reactivation, indicating that Tm-TNF sustains immune pressure as in WT mice. However, Tm-TNF mice show susceptibility to long term M. tuberculosis reactivation associated with uncontrolled influx of leukocytes in the lungs and reduced IL-12p70, IFNc and IL-10, enlarged granuloma structures, and failure to contain mycobacterial replication relative to WT mice. In conclusion, we demonstrate that both solTNF and Tm-TNF are required for maintaining immune pressure to contain reactivating M. tuberculosis bacilli even after mycobacteria-specific immunity has been established. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
10. Protective role of membrane tumour necrosis factor in the host’s resistance to mycobacterial infection.
- Author
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Allie, Nasiema, Alexopoulou, Lena, Quesniaux, Valerie J. F., Fick, Lizette, Kranidioti, Ksanthi, Kollias, George, Ryffel, Bernhard, and Jacobs, Muazzam
- Subjects
TUMOR necrosis factors ,MYCOBACTERIUM bovis ,MYCOBACTERIAL diseases ,GRANULOMA ,TUBERCULOSIS - Abstract
Tumour necrosis factor-α (TNF-α) plays a critical role in the recruitment and activation of mononuclear cells in mycobacterial infection. The role of membrane TNF, in host resistance against Mycobacterium bovis bacille Calmette–Guérin (BCG), was tested in knock-in mice in which the endogenous TNF was replaced by a non-cleavable and regulated allele (Δ1–12, TNF
tm/tm ). While 100% of mice with complete TNF deficiency (TNF−/− ) succumbed to infection, 50% of TNFtm/tm mice were able to control M. bovis BCG infection and survived the experimental period. Membrane expressed TNF allowed a substantial recruitment of activated T cells and macrophages with granuloma formation and expression of bactericidal inducible nitric oxide synthase (iNOS). Using virulent Mycobacterium tuberculosis infection we confirm that membrane TNF conferred partial protection. Infection in TNFtm/tm double transgenic mice with TNF-R1 or TNF-R2 suggest protection is mediated through TNF-R2 signalling. Therefore, the data suggest that membrane-expressed TNF plays a critical role in host defence to mycobacterial infection and may partially substitute for soluble TNF. [ABSTRACT FROM AUTHOR]- Published
- 2008
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11. Membrane TNF confers protection to acute mycobacterial infection.
- Author
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Fremond, Cecile, Allie, Nasiema, Dambuza, Ivy, Grivennikov, Sergei I., Yeremeev, Vladimir, Quesniaux, Valerie F. J., Jacobs, Muazzam, and Ryffel, Bernhard
- Subjects
TUMOR necrosis factors ,MYCOBACTERIAL diseases ,LYMPHOCYTES ,IMMUNE system ,LUNG diseases ,BIOLOGICAL membranes - Abstract
Background: Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF). Methods: C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice. Results: While TNF-KO mice succumbed to infection within 4-5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice. Conclusion: Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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12. Immuno-regulatory role of TNF in central nervous system tuberculosis.
- Author
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Sebesho, Boipelo, Kellaway, Lauriston, and Jacobs, Muazzam
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IMMUNOMODULATORS , *TUMOR necrosis factors , *CENTRAL nervous system diseases , *TUBERCULOSIS , *NEUROIMMUNOLOGY - Published
- 2014
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13. Soluble TNFRp75 regulates host protective immunity against Mycobacterium tuberculosis.
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Keeton, Roanne, Allie, Nasiema, Dambuza, Ivy, Abel, Brian, Nai-Jen Hsu, Sebesho, Boipelo, Randall, Philippa, Burger, Patricia, Fick, Elizabeth, Quesniaux, Valerie F. J., Ryffel, Bernhard, and Jacobs, Muazzam
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MYCOBACTERIUM tuberculosis , *TUBERCULOSIS -- Immunological aspects , *TUMOR necrosis factors , *THERAPEUTIC use of cytokines , *GENE expression , *THERAPEUTICS - Abstract
Development of host protective immunity against Mycobacterium tuberculosis infection is critically dependent on the inflammatory cytokine TNF. TNF signals through 2 receptors, TNFRp55 and TNFRp75; however, the role of TNFRp75-dependent signaling in immune regulation is poorly defined. Here we found that mice lacking TNFRp75 exhibit greater control of M. tuberculosis infection compared with WT mice. TNFRp75-/- mice developed effective bactericidal granulomas and demonstrated increased pulmonary recruitment of activated DCs. Moreover, IL-12p40-dependent migration of DCs to lung draining LNs of infected TNFRp75-/- mice was substantially higher than that observed in WT M. tuberculosis--infected animals and was associated with enhanced frequencies of activated M. tuberculosis--specific IFN-γ--expressing CD4+ T cells. In WT mice, TNFRp75 shedding correlated with markedly reduced bioactive TNF levels and IL-12p40 expression. Neutralization of TNFRp75 in M. tuberculosis--infected WT BM-derived DCs (BMDCs) increased production of bioactive TNF and IL-12p40 to a level equivalent to that produced by TNFRp75-/- BMDCs. Addition of exogenous TNFRp75 to TNFRp75-/- BMDCs infected with M. tuberculosis decreased IL-12p40 synthesis, demonstrating that TNFRp75 shedding regulates DC activation. These data indicate that TNFRp75 shedding downmodulates protective immune function and reduces host resistance and survival; therefore, targeting TNFRp75 may be beneficial for improving disease outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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