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 Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins

2000 ◽  
Vol 20 (3) ◽  
pp. 912-918 ◽  
Author(s):  
Patricia Greenwel ◽  
Shizuko Tanaka ◽  
Dmitri Penkov ◽  
Wen Zhang ◽  
Michelle Olive ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Type I Collagen ◽  
Type I ◽  
Necrosis Factor Alpha ◽  
Gene Coding ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

ABSTRACT Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-α inhibits transcription of the gene coding for the α2 chain of type I collagen [α2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-α-responsive element. This conclusion was based on the concomitant identification of C/EBPβ and C/EBPδ as TNF-α-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-α inhibition of α2(I) collagen but not TNF-α stimulation of the MMP-13 protease. The DN protein also blocked TNF-α downregulation of the gene coding for the α1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-α-induced signaling pathway that controls ECM formation and remodeling.

scholarly journals Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

2011 ◽  
Vol 79 (7) ◽  
pp. 2597-2607 ◽  
Author(s):  
Poonam Dharmani ◽  
Jaclyn Strauss ◽  
Christian Ambrose ◽  
Emma Allen-Vercoe ◽  
Kris Chadee
Keyword(s):  
Tumor Necrosis ◽  
Bacterial Species ◽  
Fusobacterium Nucleatum ◽  
Mucin Secretion ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Colonic Cells ◽  
Necrosis Factor

ABSTRACTThe etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial speciesFusobacterium nucleatumis a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasiveF. nucleatumisolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only liveF. nucleatuminduced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasiveF. nucleatumisolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal thatF. nucleatummay represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

scholarly journals Brucella abortus Invasion of Osteocytes Modulates Connexin 43 and Integrin Expression and Induces Osteoclastogenesis via Receptor Activator of NF-κB Ligand and Tumor Necrosis Factor Alpha Secretion

2015 ◽  
Vol 84 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Ayelén Ivana Pesce Viglietti ◽  
Paula Constanza Arriola Benitez ◽  
María Virginia Gentilini ◽  
Lis Noelia Velásquez ◽  
Carlos Alberto Fossati ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Brucella Abortus ◽  
Connexin 43 ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Receptor Activator ◽  
Factor Alpha ◽  
Necrosis Factor

Osteoarticular brucellosis is the most common localization of human active disease. Osteocytes are the most abundant cells of bone. They secrete factors that regulate the differentiation of both osteoblasts and osteoclasts during bone remodeling. The aim of this study is to determine ifBrucella abortusinfection modifies osteocyte function. Our results indicate thatB. abortusinfection induced matrix metalloproteinase 2 (MMP-2), receptor activator for NF-κB ligand (RANKL), proinflammatory cytokines, and keratinocyte chemoattractant (KC) secretion by osteocytes. In addition, supernatants fromB. abortus-infected osteocytes induced bone marrow-derived monocytes (BMM) to undergo osteoclastogenesis. Using neutralizing antibodies against tumor necrosis factor alpha (TNF-α) or osteoprotegerin (OPG), RANKL's decoy receptor, we determined that TNF-α and RANKL are involved in osteoclastogenesis induced by supernatants fromB. abortus-infected osteocytes. Connexin 43 (Cx43) and the integrins E11/gp38, integrin-α, integrin-β, and CD44 are involved in cell-cell interactions necessary for osteocyte survival.B. abortusinfection inhibited the expression of Cx43 but did not modify the expression of integrins. Yet the expression of both Cx43 and integrins was inhibited by supernatants fromB. abortus-infected macrophages.B. abortusinfection was not capable of inducing osteocyte apoptosis. However, supernatants fromB. abortus-infected macrophages induced osteocyte apoptosis in a dose-dependent manner. Taken together, our results indicate thatB. abortusinfection could alter osteocyte function, contributing to bone damage.

scholarly journals Interaction of the CD43 Sialomucin with the Mycobacterium tuberculosis Cpn60.2 Chaperonin Leads to Tumor Necrosis Factor Alpha Production

2017 ◽  
Vol 85 (3) ◽  
Author(s):  
Alvaro Torres-Huerta ◽  
Tomás Villaseñor ◽  
Angel Flores-Alcantar ◽  
Cristina Parada ◽  
Estefanía Alemán-Navarro ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Mycobacterium tuberculosis is the causal agent of tuberculosis. Tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) secreted by activated macrophages and lymphocytes are considered essential to contain Mycobacterium tuberculosis infection. The CD43 sialomucin has been reported to act as a receptor for bacilli through its interaction with the chaperonin Cpn60.2, facilitating mycobacterium-macrophage contact. We report here that Cpn60.2 induces both human THP-1 cells and mouse-derived bone marrow-derived macrophages (BMMs) to produce TNF-α and that this production is CD43 dependent. In addition, we present evidence that the signaling pathway leading to TNF-α production upon interaction with Cpn60.2 requires active Src family kinases, phospholipase C-γ (PLC-γ), phosphatidylinositol 3-kinase (PI3K), p38, and Jun N-terminal protein kinase (JNK), both in BMMs and in THP-1 cells. Our data highlight the role of CD43 and Cpn60.2 in TNF-α production and underscore an important role for CD43 in the host-mycobacterium interaction.

scholarly journals Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces Soluble Tumor Necrosis Factor Receptor Production through Tumor Necrosis Factor Alpha-Converting Enzyme Activation

2012 ◽  
Vol 80 (11) ◽  
pp. 3858-3868 ◽  
Author(s):  
Jillian M. Richmond ◽  
Elizabeth R. Duffy ◽  
Jinhee Lee ◽  
Kavon Kaboli ◽  
Daniel G. Remick ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTPrimaryMycobacterium tuberculosisinfection results in granuloma formation in lung tissue. A granuloma encapsulates mycobacterium-containing cells, thereby preventing dissemination and further infection. Tumor necrosis factor alpha (TNF-α) is a host-protective cytokine duringM. tuberculosisinfection due to its role in promoting and sustaining granuloma formation. TNF activity is regulated through the production of soluble TNF receptors (sTNFRI and sTNFRII). Therefore, we examined the potential production of endogenous sTNFRs duringM. tuberculosisinfection. Using the murine model of aerosolM. tuberculosisinfection, we determined that levels of sTNFR production were elevated in bronchoalveolar lavage fluid 1 month following infection. An investigation ofM. tuberculosiscell wall components identified that the known virulence factor mannose-capped lipoarabinomannan (ManLAM) was sufficient to induce sTNFR production, with sTNFRII being produced preferentially compared with sTNFRI. ManLAM stimulated the release of sTNFRs without TNF production, which corresponded to an increase in TNF-α-converting enzyme (TACE) activity. To determine the relevance of these findings, serum samples fromM. tuberculosis-infected patients were tested and found to have an increase in the sTNFRII/sTNFRI ratio. These data identify a mechanism by whichM. tuberculosisinfection can promote the neutralization of TNF and furthermore suggest the potential use of the sTNFRII/sTNFRI ratio as an indicator of tuberculosis disease.

scholarly journals In VitroInfection of Bovine Monocytes with Mycoplasma bovis Delays Apoptosis and Suppresses Production of Gamma Interferon and Tumor Necrosis Factor Alpha but Not Interleukin-10

2013 ◽  
Vol 82 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Musa Mulongo ◽  
Tracy Prysliak ◽  
Erin Scruten ◽  
Scott Napper ◽  
Jose Perez-Casal
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Mycoplasma Bovis ◽  
Blood Monocytes ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTMycoplasma bovisis one of the major causative pathogens of bovine respiratory complex disease (BRD), which is characterized by enzootic pneumonia, mastitis, pleuritis, and polyarthritis.M. bovisenters and colonizes bovine respiratory epithelial cells through inhalation of aerosol from contaminated air. The nature of the interaction betweenM. bovisand the bovine innate immune system is not well understood. We hypothesized thatM. bovisinvades blood monocytes and regulates cellular function to support its persistence and systemic dissemination. We used bovine-specific peptide kinome arrays to identify cellular signaling pathways that could be relevant toM. bovis-monocyte interactionsin vitro. We validated these pathways using functional, protein, and gene expression assays. Here, we show that infection of bovine blood monocytes withM. bovisdelays spontaneous or tumor necrosis factor alpha (TNF-α)/staurosporine-driven apoptosis, activates the NF-κB p65 subunit, and inhibits caspase-9 activity. We also report thatM. bovis-infected bovine monocytes do not produce gamma interferon (IFN-γ) and TNF-α, although the level of production of interleukin-10 (IL-10) is elevated. Our findings suggest thatM. bovistakes over the cellular machinery of bovine monocytes to prolong bacterial survival and to possibly facilitate subsequent systemic distribution.

scholarly journals Genome Sequence Announcement of Bacillus paranthracis Strain ICIS-279, Isolated from Human Intestine

2019 ◽  
Vol 8 (44) ◽  
Author(s):  
Oleg V. Bukharin ◽  
Natalia B. Perunova ◽  
Sergey V. Andryuschenko ◽  
Elena V. Ivanova ◽  
Taisia A. Bondarenko ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Noncoding Rna ◽  
Tumor Necrosis ◽  
Human Feces ◽  
Necrosis Factor Alpha ◽  
Sequence Announcement ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

This report describes the genome sequence of Bacillus paranthracis strain ICIS-279, isolated from human feces. It demonstrates a tumor necrosis factor alpha (TNF-α) inhibitory activity up to 0.1 ng/ml. The genome size is 5,180,499 bp, with a G+C content of 35.4%. Annotation revealed 5,168 coding sequences, including 5,168 proteins and 43 rRNA, 102 tRNA, and 5 noncoding RNA (ncRNA) genes.

scholarly journals Tumor Necrosis Factor Alpha Production from CD8+T Cells Mediates Oviduct Pathological Sequelae following Primary Genital Chlamydia muridarum Infection

2011 ◽  
Vol 79 (7) ◽  
pp. 2928-2935 ◽  
Author(s):  
Ashlesh K. Murthy ◽  
Weidang Li ◽  
Bharat K. R. Chaganty ◽  
Sangamithra Kamalakaran ◽  
M. Neal Guentzel ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Chlamydia Muridarum ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTThe immunopathogenesis ofChlamydia trachomatis-induced oviduct pathological sequelae is not well understood. Mice genetically deficient in perforin (perforin−/−mice) or tumor necrosis factor alpha (TNF-α) production (TNF-α−/−mice) displayed comparable vaginal chlamydial clearance rates but significantly reduced oviduct pathology (hydrosalpinx) compared to that of wild-type mice. Since both perforin and TNF-α are effector mechanisms of CD8+T cells, we evaluated the role of CD8+T cells during genitalChlamydia muridaruminfection and oviduct sequelae. Following vaginal chlamydial challenge, (i) mice deficient in TAP I (and therefore the major histocompatibility complex [MHC] I pathway and CD8+T cells), (ii) wild-type mice depleted of CD8+T cells, and (iii) mice genetically deficient in CD8 (CD8−/−mice) all displayed similar levels of vaginal chlamydial clearance but significantly reduced hydrosalpinx, compared to those of wild-type C57BL/6 mice, suggesting a role for CD8+T cells in chlamydial pathogenesis. Repletion of CD8−/−mice with wild-type or perforin−/−, but not TNF-α−/−, CD8+T cells at the time of challenge restored hydrosalpinx to levels observed in wild-type C57BL/6 mice, suggesting that TNF-α production from CD8+T cells is important for pathogenesis. Additionally, repletion of TNF-α−/−mice with TNF-α+/+CD8+T cells significantly enhanced the incidence of hydrosalpinx and oviduct dilatation compared to those of TNF-α−/−mice but not to the levels found in wild-type mice, suggesting that TNF-α production from CD8+T cells and non-CD8+cells cooperates to induce optimal oviduct pathology following genital chlamydial infection. These results provide compelling new evidence supporting the contribution of CD8+T cells and TNF-α production toChlamydia-induced reproductive tract sequelae.

scholarly journals Tumor Necrosis Factor Alpha Induction of NF-κB Requires the Novel Coactivator SIMPL

2004 ◽  
Vol 24 (21) ◽  
pp. 9317-9326 ◽  
Author(s):  
Hyung-Joo Kwon ◽  
Erin Haag Breese ◽  
Eva Vig-Varga ◽  
Yong Luo ◽  
Younghee Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Type I ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT A myriad of stimuli including proinflammatory cytokines, viruses, and chemical and mechanical insults activate a kinase complex composed of IκB kinase β (IKK-β), IKK-α, and IKK-γ/N, leading to changes in NF-κB-dependent gene expression. However, it is not clear how the NF-κB response is tailored to specific cellular insults. Signaling molecule that interacts with mouse pelle-like kinase (SIMPL) is a signaling component required for tumor necrosis factor alpha (TNF-α)-dependent but not interleukin-1-dependent NF-κB activation. Herein we demonstrate that nuclear localization of SIMPL is required for type I TNF receptor-induced NF-κB activity. SIMPL interacts with nuclear p65 in a TNF-α-dependent manner to promote endogenous NF-κB-dependent gene expression. The interaction between SIMPL and p65 enhances p65 transactivation activity. These data support a model in which TNF-α activation of NF-κB dependent-gene expression requires nuclear relocalization of p65 as well as nuclear relocalization of SIMPL, generating a TNF-α-specific induction of gene expression.

scholarly journals A 20-Mer Peptide Derived from the Lectin Domain of SP-A2 Decreases Tumor Necrosis Factor Alpha Production during Mycoplasma pneumoniae Infection

2020 ◽  
Vol 88 (9) ◽  
Author(s):  
Usir S. Younis ◽  
Hong Wei Chu ◽  
Monica Kraft ◽  
Julie G. Ledford
Keyword(s):  
Amino Acid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Lectin Domain ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Human surfactant protein-A2 (hSP-A2) is a component of pulmonary surfactant that plays an important role in the lung’s immune system by interacting with viruses, bacteria, and fungi to facilitate pathogen clearance and by downregulating inflammatory responses after an allergic challenge. Genetic variation in SP-A2 at position Gln223Lys is present in up to ∼30% of the population and has been associated with several lung diseases, such as asthma, pulmonary fibrosis, and lung cancer (M. M. Pettigrew, J. F. Gent, Y. Zhu, E. W. Triche, et al., BMC Med Genet 8:15, 2007, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-8-15; Y. Wang, P. J. Kuan, C. Zing, J. T. Cronkhite, et al., Am J Hum Genet 84:52–59, 2009, https://www.cell.com/ajhg/fulltext/S0002-9297(08)00595-8). Previous work performed by our group showed differences in levels of SP-A binding to non-live mycoplasma membrane fractions that were dependent on the presence of a lysine (K) or a glutamine (Q) at amino acid position 223 in the carbohydrate region of SP-A2. On the basis of these differences, we have derived 20-amino-acid peptides flanking this region of interest in order to test the ability of each to regulate various immune responses to live Mycoplasma pneumoniae in SP-A knockout mice and RAW 264.7 cells. In both models, the 20-mer containing 223Q significantly decreased both tumor necrosis factor alpha (TNF-α) mRNA levels and protein levels in comparison to the 20-mer containing 223K during M. pneumoniae infection. While neither of the 20-mer peptides (223Q and 223K) had an effect on p38 phosphorylation during M. pneumoniae infection, the 223Q-20mer peptide significantly reduced NF-κB p65 phosphorylation in both models. Taken together, our data suggest that small peptides derived from the lectin domain of SP-A2 that contain the major allelic variant (223Q) maintain activity in reducing TNF-α induction during M. pneumoniae infection.

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