scholarly journals Leishmania major Abrogates Gamma Interferon-Induced Gene Expression in Human Macrophages from a Global Perspective

2007 ◽  
Vol 75 (7) ◽  
pp. 3506-3515 ◽  
Author(s):  
Nisha Dogra ◽  
Corinna Warburton ◽  
W. Robert McMaster
Keyword(s):  
Gene Expression ◽  
Host Cell ◽  
Large Scale ◽  
Leishmania Major ◽  
Gamma Interferon ◽  
Receptor Expression ◽  
Global Perspective ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Ifn Γ

ABSTRACT Infection with Leishmania major triggers several pathways in the host cell that are crucial to initial infection as well as those that are used by Leishmania to enhance its replication and virulence. To identify the molecular events of the host cell in response to Leishmania, the global gene expression of the human monocytic cell line THP-1 either infected with Leishmania major in the presence and absence of gamma interferon (IFN-γ) or in the presence of IFN-γ alone was analyzed using high-density human oligonucleotide microarrays, followed by statistical analysis. The persistence of the parasite despite an extensive response to IFN-γ, added 24 h after infection with L. major, suggests that L. major can survive in an IFN-γ-enriched environment in vitro. Results demonstrate that L. major counteracts the IFN-γ response in macrophages on a large scale. Expression of genes involved in the innate immune response, cell adhesion, proteasomal degradation, Toll-like receptor expression, a variety of signaling molecules, and matrix metalloproteinases was significantly modulated.

scholarly journals Genomic Profiling of a Human Leukemic Monocytic Cell-Line (THP-1) Exposed to Alpha Particle Radiation

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Vinita Chauhan ◽  
Matthew Howland
Keyword(s):  
Gene Expression ◽  
Radiation Effects ◽  
Assessment Tool ◽  
Late Onset ◽  
Dose Range ◽  
Biological Assessment ◽  
Global Changes ◽  
Monocytic Cell ◽  
Particle Radiation ◽  
Monocytic Cell Line

This study examined alpha (α-) particle radiation effects on global changes in gene expression in human leukemic monocytic cells (THP-1) for the purposes of mining for candidate biomarkers that could be used for the development of a biological assessment tool. THP-1 cells were exposed toα-particle radiation at a dose range of 0 to 1.5 Gy. Twenty-four hours and three days after exposure gene expression was monitored using microarray technology. A total of 16 genes were dose responsive and classified as early onset due to their expression 24 h after exposure. Forty-eight transcripts were dose responsive and classified as late-onset as they were expressed 72 h after exposure. Among these genes, 6 genes were time and dose responsive and validated further using alternate technology. These transcripts were upregulated and associated with biological processes related to immune function, organelle stability and cell signalling/communication. This panel of genes merits further validation to determine if they are strong candidate biomarkers indicative ofα-particle exposure.

scholarly journals Staphylococcal Enterotoxin B In Vivo Modulates both Gamma Interferon Receptor Expression and Ligand-Induced Activation of Signal Transducer and Activator of Transcription 1 in T Cells

2006 ◽  
Vol 75 (1) ◽  
pp. 306-313 ◽  
Author(s):  
R. Plaza ◽  
J. L. Rodriguez-Sanchez ◽  
C. Juarez
Keyword(s):  
T Cells ◽  
Gamma Interferon ◽  
Staphylococcal Enterotoxin ◽  
Receptor Expression ◽  
Protective Mechanism ◽  
Staphylococcal Enterotoxin B ◽  
Selective Blockade ◽  
Stat1 Signaling ◽  
Ifn Γ ◽  
Enterotoxin B

ABSTRACT Superantigens (SAg) are bacterial exotoxins that provoke extreme responses in the immune system; for example, the acute hyperactivation of SAg-reactive T cells that leads to toxic shock syndrome is followed within days by strong immunosuppression. The gamma interferon (IFN-γ) response is deeply affected in both extremes. The implication of IFN-γ in the pathophysiology of lethal shock induced in mice after a secondary challenge with the SAg staphylococcal enterotoxin B (SEB) prompted us to study the regulation of IFN-γ secretion and the intracellular response. We demonstrate in this study that a rechallenge with SEB becomes lethal only when given inside a critical time window after SEB priming and is associated with an increase of IFN-γ serum release 72 h after priming. However, at this time, a selective blockade of IFN-γ/STAT1 signaling develops in spleen cells, correlating with a lack of expression of the IFN-γ receptor beta subunit and STAT1 in the T-cell population. Selective blockade of the STAT1 signaling pathway—while simultaneously maintaining STAT3 signaling and expression—may be a protective mechanism that shortens IFN-γ production during the Th1 effector response. This blockade may also have consequences on switching towards a suppressor phenotype with chronic exposure to the superantigen.

scholarly journals Repression of human cytomegalovirus major immediate early gene expression in a monocytic cell line

1992 ◽  
Vol 73 (2) ◽  
pp. 433-435 ◽  
Author(s):  
J. H. Sinclair ◽  
J. Baillie ◽  
L. A. Bryant ◽  
J. A. Taylor-Wiedeman ◽  
J. G. P. Sissons
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Human Cytomegalovirus ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Early Gene Expression

IFN-γ Is an Essential Cosignal for Triggering IFN-β2/BSF-2/IL-6 Gene Expression in Human Monocytic Cell Linesa,b

2008 ◽  
Vol 557 (1) ◽  
pp. 130-143 ◽  
Author(s):  
JOSIANE SANCEAU ◽  
FLORENCE BERANGER ◽  
CORINNE GAUDELET ◽  
JUANA WIETZERBIN
Keyword(s):  
Gene Expression ◽  
Monocytic Cell ◽  
Human Monocytic Cell ◽  
Ifn Γ

scholarly journals The Gamma Interferon (IFN-γ)-Inducible GTP-Binding Protein IGTP Is Necessary for Toxoplasma Vacuolar Disruption and Induces Parasite Egression in IFN-γ-Stimulated Astrocytes

2008 ◽  
Vol 76 (11) ◽  
pp. 4883-4894 ◽  
Author(s):  
T. Melzer ◽  
A. Duffy ◽  
L. M. Weiss ◽  
S. K. Halonen
Keyword(s):  
Host Cell ◽  
Fluorescent Protein ◽  
Binding Protein ◽  
Parasitophorous Vacuole ◽  
Central Nervous System Infection ◽  
Gamma Interferon ◽  
Gtp Binding Protein ◽  
Gtp Binding ◽  
Ifn Γ ◽  
Green Fluorescent

ABSTRACT Toxoplasma gondii is a common central nervous system infection in individuals with immunocompromised immune systems, such as AIDS patients. Gamma interferon (IFN-γ) is the main cytokine mediating protection against T. gondii. Our previous studies found that IFN-γ significantly inhibits T. gondii in astrocytes via an IFN-γ-inducible GTP-binding protein (IGTP)-dependent mechanism. The IGTP-dependent-, IFN-γ-stimulated inhibition is not understood, but recent studies found that IGTP induces disruption of the parasitophorous vacuole (PV) in macrophages. In the current study, we have further investigated the mechanism of IFN-γ inhibition and the role of IGTP in the vacuolar disruption in murine astrocytes. Vacuolar disruption was found to be dependent upon IGTP, as PV disruption was not observed in IGTP-deficient (IGTP−/−) astrocytes and PV disruption could be induced in IGTP−/− astrocytes transfected with IGTP. Live-cell imaging studies using green fluorescent protein-IGTP found that IGTP is delivered to the PV via the host cell endoplasmic reticulum (ER) early after invasion and that IGTP condenses into vesicle-like structures on the vacuole just prior to PV disruption, suggesting that IGTP is involved in PV disruption. Intravacuolar movement of the parasite occurred just prior to PV disruption. In some instances, IFN-γ induced parasite egression. Electron microscopy and immunofluorescence studies indicate that the host cell ER fuses with the PV prior to vacuolar disruption. On the basis of these results, we postulate a mechanism by which ER/PV fusion is a crucial event in PV disruption. Fusion of the ER with the PV, releasing calcium into the vacuole, may also be the mechanism by which intravacuolar parasite movement and IFN-γ-induced parasite egression occur.

scholarly journals Genome-wide profiling of transcribed enhancers during macrophage activation

2017 ◽  
Author(s):  
Elena Denisenko ◽  
Reto Guler ◽  
Musa Mhlanga ◽  
Harukazu Suzuki ◽  
Frank Brombacher ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Large Scale ◽  
Transcriptional Control ◽  
Macrophage Activation ◽  
Transcriptional Responses ◽  
Protein Coding ◽  
Genome Wide ◽  
Ifn Γ ◽  
Cap Analysis

AbstractMacrophages are sentinel cells essential for tissue homeostasis and host defence. Owing to their plasticity, macrophages acquire a range of functional phenotypes in response to microenvironmental stimuli, of which M(IFN-γ) and M(IL-4/IL-13) are well-known for their opposing pro- and anti-inflammatory roles. Enhancers have emerged as regulatory DNA elements crucial for transcriptional activation of gene expression. Using cap analysis of gene expression and epigenetic data, we identify on large-scale transcribed enhancers in mouse macrophages, their time kinetics and target protein-coding genes. We observe an increase in target gene expression, concomitant with increasing numbers of associated enhancers and find that genes associated to many enhancers show a shift towards stronger enrichment for macrophage-specific biological processes. We infer enhancers that drive transcriptional responses of genes upon M(IFN-γ) and M(IL-4/IL-13) macrophage activation and demonstrate stimuli-specificity of regulatory associations. Finally, we show that enhancer regions are enriched for binding sites of inflammation-related transcription factors, suggesting a link between stimuli response and enhancer transcriptional control. Our study provides new insights into genome-wide enhancer-mediated transcriptional control of macrophage genes, including those implicated in macrophage activation, and offers a detailed genome-wide catalogue to further elucidate enhancer regulation in macrophages.

scholarly journals Enhanced Replication of Leishmania amazonensis Amastigotes in Gamma Interferon-Stimulated Murine Macrophages: Implications for the Pathogenesis of Cutaneous Leishmaniasis

2004 ◽  
Vol 72 (2) ◽  
pp. 988-995 ◽  
Author(s):  
Hai Qi ◽  
Jiaxiang Ji ◽  
Nanchaya Wanasen ◽  
Lynn Soong
Keyword(s):  
Leishmania Major ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Leishmania Amazonensis ◽  
Promoting Effect ◽  
Necrosis Factor Alpha ◽  
Different Temperatures ◽  
Ifn Γ

ABSTRACT During Leishmania major infection in mice, gamma interferon (IFN-γ) plays an essential role in controlling parasite growth and disease progression. In studies designed to ascertain the role of IFN-γ in Leishmania amazonensis infection, we were surprised to find that IFN-γ could promote L. amazonensis amastigote replication in macrophages (MΦs), although it activated MΦs to kill promastigotes. The replication-promoting effect of IFN-γ on amastigotes was independent of the source and genetic background of MΦs, was apparently not affected by surface opsonization of amastigotes, was not mediated by interleukin-10 or transforming growth factor β, and was observed at different temperatures. Consistent with the different fates of promastigotes and amastigotes in IFN-γ-stimulated MΦs, L. amazonensis-specific Th1 transfer helped recipient mice control L. amazonensis infection established by promastigotes but not L. amazonensis infection established by amastigotes. On the other hand, IFN-γ could stimulate MΦs to limit amastigote replication when it was coupled with lipopolysaccharides but not when it was coupled with tumor necrosis factor alpha. Thus, IFN-γ may play a bidirectional role at the level of parasite-MΦ interactions; when it is optimally coupled with other factors, it has a protective effect against infection, and in the absence of such synergy it promotes amastigote growth. These results reveal a quite unexpected aspect of the L. amazonensis parasite and have important implications for understanding the pathogenesis of the disease and for developing vaccines and immunotherapies.

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